The marriage of Bouvier's parents was strained by her father's alcoholism and extramarital affairs; the family had also struggled with financial difficulties following the Wall Street Crash of 1929. They separated in 1936 and divorced four years later, with the press publishing intimate details of the split. According to her cousin John H. Davis, Bouvier was deeply affected by the divorce and subsequently had a "tendency to withdraw frequently into a private world of her own". When her mother married Standard Oil heir Hugh Dudley Auchincloss, Jr., Bouvier and her sister did not attend the ceremony, because it was arranged quickly and travel was restricted due to World War II. Bouvier gained three step-siblings from Auchincloss' two previous marriages, Hugh "Yusha" Auchincloss III, Thomas Gore Auchincloss, and Nina Gore Auchincloss; she formed the closest bond with Yusha, who became one of her most trusted confidants. The marriage later produced two more children, Janet Jennings Auchincloss in 1945 and James Lee Auchincloss in 1947.

In 1935, Bouvier enrolled in Manhattan's Chapin School, which she attended for grades 1–6. She was a bright student but often misbehaved; one of her teachers described her as "a darling child, the prettiest little girl, very clever, very artistic, and full of the devil". Bouvier's mother attributed her daughter's behavior to the way that she finished her assignments ahead of classmates and then acted out in boredom. Her behavior improved after the headmistress warned her that none of her positive qualities would matter if she did not behave.

Jacqueline had visited the White House twice prior to becoming First Lady, the first time as a grade-school tourist in 1941 and again as the guest of Mamie Eisenhower shortly before her husband's inauguration. She was dismayed to find that the mansion's rooms were furnished with undistinguished pieces that displayed little historical significance and made it her first major project as First Lady to restore its historical character. On her first day in residence, she began her efforts with the help of interior decorator Sister Parish. She decided to make the family quarters attractive and suitable for family life by adding a kitchen on the family floor and new rooms for her children. The $50,000 that had been appropriated for this effort was almost immediately exhausted. Continuing the project, she established a fine arts committee to oversee and fund the restoration process and solicited the advice of early American furniture expert Henry du Pont. To solve the funding Problem, a White House guidebook was published, sales of which were used for the restoration. Working with Rachel Lambert Mellon, Kennedy also oversaw the redesign and replanting of the White House Rose Garden and the East Garden, which was renamed the Jacqueline Kennedy Garden after her husband's assassination. In addition, Kennedy helped to stop the destruction of historic homes in Lafayette Square in Washington, D.C., because she felt these buildings were an important part of the nation's capital and played an essential role in its history.

After six years at Chapin, Bouvier attended the Holton-Arms School in North West Washington, D.C. from 1942 to 1944, and Miss Porter's School in Farmington, Connecticut, from 1944 to 1947. She chose Miss Porter's because it was a boarding school that allowed her to distance herself from the Auchinclosses, and because the school placed an emphasis on college preparatory classes. In her senior class yearbook, Bouvier was acknowledged for "her wit, her accomplishment as a horsewoman, and her unwillingness to become a housewife". Jacqueline later hired her childhood friend Nancy Tuckerman to be her Social Secretary at the White House. She graduated among the top students of her class and received the Maria McKinney Memorial Award for Excellence in Literature.

In the fall of 1947, Bouvier entered Vassar College in Poughkeepsie, New York. She had wanted to attend Sarah Lawrence College, closer to New York City, but her parents insisted that she choose the more geographically isolated Vassar. Bouvier was an accomplished student who participated in the school's art and drama clubs and wrote for its newspaper. Due to her dislike for the college, she did not take an active part in its social life and instead traveled back to Manhattan on the weekends. She had made her society debut in the summer before entering college and became a frequent presence in New York social functions. Hearst columnist Igor Cassini dubbed her the "debutante of the year". Bouvier spent her junior year (1949–1950) in France—at the University of Grenoble in Grenoble, and at the Sorbonne in Paris—in a study-abroad program through Smith College. Upon returning home, she transferred to George Washington University in Washington, D.C., graduating with a Bachelor of Arts degree in French literature in 1951. During the early years of her marriage to John F. Kennedy, she took continuing education classes in American history at Georgetown University in Washington, D.C.

Bouvier was the elder daughter of Wall Street stockbroker John Vernou Bouvier III and socialite Janet Lee Bouvier. In 1951, she graduated with a Bachelor of Arts degree in French literature from George Washington University and went on to work for the Washington Times-Herald as an inquiring Photographer.

Bouvier moved back to Merrywood and was hired as a part-time receptionist at the Washington Times-Herald. A week later, she approached Editor Frank Waldrop and requested more challenging work; she was given the position of "Inquiring Camera Girl", despite Waldrop's initial concerns about her competence. The position required her to pose witty questions to individuals chosen at random on the street and take their pictures for publication in the newspaper alongside selected quotations from their responses. In addition to the random "man on the street" vignettes, she sometimes sought interviews with people of interest, such as six-year-old Tricia Nixon. Bouvier interviewed Tricia a few days after her father Richard Nixon was elected to the vice presidency in the 1952 election. During this time, Bouvier was also briefly engaged to a young stockbroker, John G. W. Husted, Jr. After only a month of dating, the couple published the announcement in The New York Times in January 1952. She called off the engagement after three months, because she had found him "immature and boring" once she got to know him better.

Bouvier and Kennedy were married on September 12, 1953, at St. Mary's Church in Newport, Rhode Island, in a mass celebrated by Boston's Archbishop Richard Cushing. The wedding was considered the social event of the season with an estimated 700 guests at the ceremony and 1200 at the reception that followed at Hammersmith Farm. The wedding dress, now housed in the Kennedy Library in Boston, Massachusetts, and the dresses of her attendants were created by designer Ann Lowe of New York City.

In her role as First Lady, Kennedy preferred to wear clean-cut suits with a skirt hem down to middle of the knee, three-quarter sleeves on notch-collar jackets, sleeveless A-line dresses, above-the-elbow gloves, low-heel pumps, and pillbox hats. Dubbed the "Jackie" look, these clothing items rapidly became fashion trends in the Western world. More than any other First Lady, her style was copied by commercial manufacturers and a large segment of young women. Her influential bouffant hairstyle, described as a "grown-up exaggeration of little girls' hair," was created by Mr. Kenneth, who worked for her from 1954 until 1986.

Jacqueline gave birth to a daughter Caroline on November 27, 1957, via Caesarean section. At the time, she and John Kennedy were campaigning for his re-election to the Senate, and they posed with their infant daughter for the cover of the April 21, 1958 issue of Life Magazine. They traveled together during the campaign, trying to narrow the geographical gap between them that had persisted for the first five years of the marriage. Soon enough, John Kennedy started to notice the value that his wife added to his congressional campaign. Kenneth O'Donnell remembered that "the size of the crowd was twice as big" when she accompanied her husband; he also recalled her as "always cheerful and obliging". John's mother Rose observed Jacqueline as not being "a natural-born campaigner" due to her shyness and being uncomfortable with too much attention. In November 1958, John Kennedy was reelected to a second term. He credited Jacqueline's visibility in both ads and stumping as vital assets in securing his victory, and he called her "simply invaluable".

In July 1959, Historian Arthur M. Schlesinger visited the Kennedy Compound in Hyannis Port and had his first conversation with Jacqueline; he found her to have "tremendous awareness, an all-seeing eye and a ruthless judgment". That year, Jack Kennedy traveled to 14 states, with Jacqueline taking long breaks from the trips so she could spend time with their daughter Caroline. She also counseled her husband on improving his wardrobe in preparation for his intended presidential campaign the following year. In particular, she traveled to Louisiana to visit Edmund Reggie and to help her husband garner support in the state for his presidential bid.

Jacqueline Kennedy became a global fashion icon during her husband's presidency. After the 1960 election, she commissioned French-born American fashion designer and Kennedy family friend Oleg Cassini to create an original wardrobe for her appearances as First Lady. From 1961 to 1963, Cassini dressed her in many of her most iconic ensembles, including her Inauguration Day fawn coat and Inaugural gala gown, as well as many outfits for her visits to Europe, India, and Pakistan. In 1961, Kennedy spent $45,446 more on fashion than the $100,000 annual salary her husband earned as President.

Jodi Balfour portrays Kennedy in the eighth episode of the second season of Netflix's original drama series, The Crown, set during the June 1961 visit of the Kennedy couple to the Buckingham Palace and the events that followed the assassination of John F. Kennedy.

At the urging of U.S. Ambassador to India John Kenneth Galbraith, Kennedy undertook a tour of India and Pakistan with her sister Lee Radziwill in 1962, which was amply documented in photojournalism of the time as well as in Galbraith's journals and memoirs. She was gifted with a horse called Sardar by the President of Pakistan, Ayub Khan, as he had found out on his visit to the White House that he and the First Lady had a Common interest in horses. Life magazine correspondent Anne Chamberlin wrote that Kennedy "conducted herself magnificently” although noting that her crowds were smaller than those that President Dwight Eisenhower and Queen Elizabeth II attracted when they had previously visited these countries. In addition to these well-publicized trips during the three years of the Kennedy administration, she traveled to countries including Afghanistan, Austria, Canada, Colombia, England, Greece, Italy, Mexico, Morocco, Turkey, and Venezuela. Unlike her husband, Kennedy was fluent in Spanish, which she used to address Latin American audiences.

On November 29, 1963—a week after her husband's assassination—Kennedy was interviewed in Hyannis Port by Theodore H. White of Life magazine. In that session, she famously compared the Kennedy years in the White House to King Arthur's mythical Camelot, commenting that the President often played the title song of Lerner and Loewe's musical recording before retiring to bed. She also quoted Queen Guinevere from the musical, trying to express how the loss felt. The era of the Kennedy administration would subsequently often be referred to as the "Camelot Era," although historians have later argued that the comparison is not appropriate, with Robert Dallek stating that Kennedy's "effort to lionize [her husband] must have provided a therapeutic shield against immobilizing grief."

After the assassination, Kennedy relied heavily on her brother-in-law Robert F. Kennedy; she observed him to be the "least like his father" of the Kennedy brothers. He had been a source of support after she had suffered a miscarriage early in her marriage; it was he, not her husband, who stayed with her in the hospital. In the aftermath of the assassination, Bobby became a surrogate father for her children until eventual demands by his own large family and his responsibilities as Attorney General required him to reduce attention. He credited Jackie with convincing him to stay in politics, and she supported his 1964 run for United States Senator from New York. According to biographer C. David Heymann, the two became romantically involved after her husband's death.

Kennedy was named to the International Best Dressed List Hall of Fame in 1965. Many of her signature clothes are preserved at the John F. Kennedy Library and Museum; pieces from the collection were exhibited at the Metropolitan Museum of Art in New York in 2001. Titled "Jacqueline Kennedy: The White House Years," the exhibition focused on her time as a First Lady.

Despite having commissioned william Manchester's authorized account of President Kennedy's death, The Death of a President, Jacqueline was subject to significant media attention in 1966–1967 when she and Robert Kennedy tried to block the publication. They sued publishers Harper & Row in December 1966; the suit was settled the following year when Manchester removed passages that detailed President Kennedy's private life. White viewed the ordeal as validation of the measures the Kennedy family, Jacqueline in particular, were prepared to take to preserve President Kennedy's public image.

During the Vietnam War in November 1967, Life magazine dubbed Kennedy "America's unofficial roving ambassador" when she and David Ormsby-Gore, former British ambassador to the United States during the Kennedy administration, traveled to Cambodia, where they visited the religious complex of Angkor Wat with Chief of State Norodom Sihanouk. According to Historian Milton Osbourne, her visit was "the start of the repair to Cambodian-US relations, which had been at a very low ebb". She also attended the funeral services of Martin Luther King, Jr. in Atlanta, Georgia, in April 1968, despite her initial reluctancy due to the crowds and reminders of President Kennedy's death.

On October 20, 1968, Kennedy married her long-time friend Aristotle Onassis, a wealthy Greek shipping magnate who was able to provide the privacy and security she sought for herself and her children. The wedding took place on Skorpios, Onassis's private Greek island in the Ionian Sea. After marrying Ari, she took the legal name Jacqueline Onassis and consequently lost her right to Secret Service protection, which is an entitlement of a widow of a U.S. President. The marriage brought her considerable adverse publicity. The fact that Aristotle was divorced and his former wife Athina Livanos was still living led to speculation that Jacqueline might be excommunicated by the Roman Catholic church, though that concern was explicitly dismissed by Boston's Archbishop, Cardinal Richard Cushing as "nonsense." She was condemned by some as a "public sinner," and became the target of paparazzi who followed her everywhere and nicknamed her "Jackie O".

In addition to her work as an Editor, Onassis participated in cultural and architectural preservation. In the 1970s, she led a historic preservation campaign to save from demolition and renovate Grand Central Terminal in New York. A plaque inside the terminal acknowledges her prominent role in its preservation. In the 1980s, she was a major figure in protests against a planned skyscraper at Columbus Circle that would have cast large shadows on Central Park; the project was cancelled. A later project proceeded despite protests: a large twin-towered skyscraper, the Time Warner Center, was completed in 2003.

After the death of her husband, Onassis returned permanently to the United States, splitting her time between Manhattan, Martha's Vineyard, and the Kennedy compound in Hyannis, Massachusetts. In 1975, she became a consulting Editor at Viking Press, a position that she held for two years.

After almost a decade of avoiding participation in political events, she attended the 1976 Democratic National Convention and stunned the assembled delegates when she appeared in the visitors' gallery. She resigned from Viking Press in 1977 following the false accusation by The New York Times that she held some responsibility for the company's publication of Jeffrey Archer novel Shall We Tell the President?, which was set in a fictional Future presidency of Ted Kennedy and described an assassination plot against him. Two years later, she appeared alongside her mother-in-law Rose Kennedy at Faneuil Hall in Boston when Ted Kennedy announced that he was going to challenge incumbent President Jimmy Carter for the Democratic nomination for President. She participated in the subsequent presidential campaign, which was unsuccessful.

Onassis remained the subject of considerable press attention, most notoriously involving the paparazzi Photographer Ron Galella, who followed her around and photographed her as she went about her day-to-day activities; he took candid photos of her without her permission. She ultimately obtained a restraining order against him, and the situation brought attention to the Problem of paparazzi photography. From 1980 until her death, Jacqueline maintained a close relationship with Maurice Tempelsman, who was her companion and personal financial adviser; he was a Belgian-born industrialist and Diamond merchant who was estranged from his wife.

Jaclyn Smith portrays Kennedy in the 1981 television film Jacqueline Bouvier Kennedy, depicting Kennedy's life until the end of the JFK presidency. The film's Producer Louis Rudolph stated an interest in creating a "positive portrait of a woman who I thought had been very much maligned," comments that were interpreted by John J. O'Connor of The New York Times as erasing any chances of critique toward Kennedy. Though Smith received praise for her performance, with Marilynn Preston calling her "convincing in an impossible role", Tom Shales wrote "Jaclyn Smith couldn't act her way out of a Gucci bag".

Blair Brown portrays Kennedy in the 1983 miniseries Kennedy, set during the Kennedy presidency. Brown used wigs and makeup to better resemble Kennedy and said through playing the role she gained a different view of the assassination: "I realized that this was a woman witnessing the public execution of her husband." Jason Bailey praised her performance, while Andrea Mullaney noted her resemblance to Kennedy and general shyness. Brown was nominated for a television BAFTA as Best Actress and a Golden Globe as Best Actress in a Miniseries or Television Film.

In the early 1990s, Onassis became a supporter of Bill Clinton and contributed money to his presidential campaign. Following the election, she met with First Lady Hillary Clinton, and advised her on raising a child in the White House. Clinton wrote in her memoir Living History, that Onassis was "a source of inspiration and advice for me". Democratic consultant Ann Lewis observed that Onassis had reached out to the Clintons "in a way she has not always acted toward leading Democrats in the past".

Marianna Bishop, Sarah Michelle Gellar, and Roma Downey portray Kennedy in the 1991 miniseries A Woman Named Jackie, covering her entire life until the death of Aristotle Onassis. Of being contacted for the role, Downey reflected: "I thought I was a strange choice because I didn't think I looked anything like her and I was Irish." Half of Downey's wardrobe was designed by Shelley Komarov and Downey stated that though she had long harbored "great respect and admiration" for Kennedy, she was unaware of the troubles in her childhood. Reviewer Rick Kogan praised Downey with doing "a surprisingly fine job in the demanding title role", while Howard Rosenberg lamented Downey's performance failing to "pierce this thick glaze of superficiality." Ability credited the role with raising Downey's profile. In 1992, the miniseries won the Emmy Award for Outstanding Miniseries.

Rhoda Griffis portrays Kennedy in the 1992 film Love Field, set shortly before and in the aftermath of JFK's assassination. It was Griffis' feature film debut. Griffis said she had been told by her orthodontist of her resemblance to Kennedy and was cast as her upon walking into the auditions for the role.

On May 23, 1994, her funeral Mass was held a few blocks away from her apartment at the Church of St. Ignatius Loyola, the Catholic parish where she was baptized in 1929 and confirmed as a teenager. She was interred at Arlington National Cemetery in Arlington, Virginia, alongside President Kennedy, their son Patrick, and their stillborn daughter Arabella. President Bill Clinton delivered a eulogy at her graveside Service. At the time of her death, Onassis was survived by her children Caroline and John Jr., three grandchildren, sister Lee Radziwill, son-in-law Edwin Schlossberg, and half-brother James Lee Auchincloss. She left an estate that its executors valued at $43.7 million.

Following her resignation from Viking Press, Onassis was hired by Doubleday, where she worked as an associate Editor under an old friend, John Turner Sargent, Sr. Among the books she edited for the company are Larry Gonick's The Cartoon History of the Universe, the English translation of the three volumes of Naghib Mahfuz's Cairo Trilogy (with Martha Levin), and autobiographies of ballerina Gelsey Kirkland, singer-songwriter Carly Simon, and fashion icon Diana Vreeland. She also encouraged Dorothy West, her neighbor on Martha's Vineyard and the last surviving member of the Harlem Renaissance, to complete the novel The Wedding (1995), a multi-generational story about race, class, wealth, and power in the U.S..

Stephanie Romanov portrays Kennedy in the 2000 film Thirteen Days, taking place during the Cuban Missile Crisis. Philip French of The Guardian noted her small role and being out of "the loop" was accurate of women's roles in "the early Sixties." Laura Clifford called Romanov "unconvincing" in the role.

Jill Hennessy portrays Kennedy in the 2001 television film Jackie, Ethel, Joan: The Women of Camelot. Hennessy prepared for the performance by watching hours of archival footage of Kennedy and cited one of the reasons for her favoring of the miniseries was its distinctiveness in not focusing "strictly on the men or only on Jackie." Reviewers Anita Gates and Terry Kelleher believed Hennessy brought "elegance" to the role while Steve Oxman panned the performance: "Hennessy simply doesn’t possess the right natural grace. But this pic has a habit of telling us more that it shows us, and the Actress manages to communicate the most important elements of the story without ever making it especially convincing."

Jacqueline Bisset portrays Onassis in the 2003 film America's Prince: The John F. Kennedy Jr. Story. Bisset noted the glasses she used during the film were holdovers from a prior role in The Greek Tycoon. Neil Genzlinger observed that Bisset "should have known better" in taking on the role while Kristen Tauer wrote Bisset portraying Onassis as a mother was a "different central light than many proceeding films".

Jeanne Tripplehorn portrays Onassis in the 2009 film Grey Gardens for a single scene. Tripplehorn said questions she had about Edith Bouvier Beale that she thought would be answered by being a part of the film remained unsolved. Tripplehorn received diverse reactions to her performance while Brian Lowry noted her resemblance to Onassis and small role.

Katie Holmes portrays Kennedy in the 2011 miniseries The Kennedys, set during the Kennedy presidency and its 2017 sequel The Kennedys: After Camelot, focusing on her life after 1968. Mary McNamara and Hank Stuever regarded Holmes' performance with neutrality in their reviews of The Kennedys while Hadley Freeman called her "bloodless" in the role. Holmes stated reprising the role was a "bigger challenge" for having to act through later periods of Kennedy's life. When asked of the concurrent Jackie film, Holmes said, "I think its really exciting. It's just is a testament to how amazing Jacqueline Kennedy Onassis was and how much she meant to our country." Holmes also stated both should be watched due to covering different periods of Jacqueline's life. In The Kennedys: After Camelot, Holmes' performance was viewed favorably by Daniel Feinberg and Allison Keane while Kristi Turnquist panned her.

In 2012, Time magazine included Kennedy on its All-TIME 100 Fashion Icons list.

Ginnifer Goodwin portrays her in the 2013 television film Killing Kennedy. Goodwin used intimate photos to better portray Kennedy and was concerned "to do her justice and to play her as accurately as possible without ever doing an impression of her." Costar Rob Lowe said of seeing Goodwin in the pink Chanel suit, "It made it real. If I were under any illusions about what we were doing, seeing her in that iconic moment was, I would say, sobering." Tom Carson wrote that Goodwin's "trademark vulnerability humanizes Jackie considerably" while Bruce Miller called her a miscast and Robert Lloyd and Brian Lowry panned her performance.

A week after the assassination, new President Lyndon Baines Johnson established the Warren Commission—led by Chief Justice Earl Warren—to investigate the assassination. Ten months later, the Commission issued its report with the finding that Lee Harvey Oswald had acted alone when he assassinated President Kennedy. Privately, his widow cared little about the investigation, stating that even if they had the right suspect, it would not bring her husband back. Nevertheless, she gave a deposition to the Warren Commission. Following the assassination and the media coverage that had focused intensely on her during and after the burial, Jacqueline stepped back from official public view, apart from a brief appearance in Washington to honor the Secret Service agent, Clint Hill, who had climbed aboard the limousine in Dallas to try to shield her and the President.

Natalie Portman portrays Kennedy in the 2016 film Jackie, set during the JFK presidency and the immediate aftermath of the assassination. Portman admitted being intimidated taking the role and doing research in preparation for filming. Nigel M. Smith wrote that by portraying Kennedy, Portman was "taking on arguably the biggest challenge of her career". Manohla Dargis, David Edelstein, and Peter Bradshaw praised her performance. Portman was nominated for Best Actress by Academy Awards, AACTA Awards, AWFJ, AFCA, and BSFC, and won the category by the Online Film Critics Society.