John Fitzgerald Kennedy Jr. was born at Georgetown University Hospital on November 25, 1960, two weeks after his father was elected President. His parents had a stillborn daughter named Arabella four years before John Jr.'s birth. John Jr. had an older sister, Caroline, and a younger brother, Patrick, who died two days after his premature birth in 1963. His putative nickname, "John-John", came from a reporter who misheard JFK calling him "John" twice in quick succession; the name was not used by his family.

John F. Kennedy Jr. was the first child ever born to a President-elect of the United States. On the occasion of the 50th anniversary of the assassination of John Jr.'s father on November 22, 1963, the New York Daily News re-ran the famous photograph of the three-year-old John Jr. saluting his father's coffin during the funeral procession. Photographer Dan Farrell, who took the photo, called it "the saddest thing I've ever seen in my whole life".

After his uncle Robert was assassinated in 1968, his mother took him and his sister out of the United States, saying: "If they're killing Kennedys, then my children are targets ... I want to get out of this country." The same year, she married Greek shipping tycoon Aristotle Onassis, and the family went to live on his private island of Skorpios. Kennedy is said to have considered his stepfather "a joke".

In 1971, Kennedy returned to the White House with his mother and sister for the first time since the assassination. President Richard Nixon's daughters gave Kennedy a tour that included his old bedroom, and Nixon showed him the Resolute desk under which his father had let him play. When Onassis died in 1975, he left Kennedy $25,000, though Jacqueline was able to renegotiate the will, and acquired $20 million for herself and her children.

In 1976, Kennedy and his cousin visited an earthquake disaster zone at Rabinal in Guatemala, helping with heavy building work and distributing food. The local priest said that they "ate what the people of Rabinal ate and dressed in Guatemalan clothes and slept in tents like most of the earthquake victims", adding that the two "did more for their country's image" in Guatemala "than a roomful of ambassadors". On his sixteenth birthday, Kennedy's Secret Service protection ended. He spent the summer of 1978 working as a wrangler in Wyoming.

By his junior year at Brown, he had moved off campus to live with several other students in a shared house, and spent time at Xenon, a club owned by Howard Stein. Kennedy was initiated into Phi Psi, a local social fraternity that had been the Rhode Island Alpha Chapter of national Phi Kappa Psi fraternity until 1978. He graduated in 1983 with a bachelor's degree in American studies, and then took a break from work, traveling to India and spending some time at the University of Delhi, where he met Mother Teresa. He also worked with some of the Kennedy special interest projects, including the East Harlem School at Exodus House and Reaching Up.

Before attending Brown University, Kennedy accompanied his mother to Africa. On a pioneering course, he rescued his group, which had gotten lost for two days without food or water, and won points for leadership. In 1979, the John F. Kennedy Presidential Library and Museum was dedicated, and Kennedy made his first major speech, reciting Stephen Spender's poem "I Think Continually of Those Who Were Truly Great".

While attending Brown University, Kennedy met Sally Munro, whom he dated for six years, and they visited India in 1983. While he was a student at Brown, he also met Brooke Shields, with whom he was later linked.

After the 1984 Democratic Convention in San Francisco, Kennedy returned to New York and earned $20,000 a year in a position at the Office of Business Development, where his boss reflected that he worked "in the same crummy cubbyhole as everybody else. I heaped on the work and was always pleased." From 1984 to 1986, he worked for the New York City Office of Business Development and served as deputy Director of the 42nd Street Development Corporation in 1986, conducting negotiations with developers and city agencies. In 1988, he became a summer associate at Manatt, Phelps, Rothenberg & Phillips, a Los Angeles law firm with strong connections to the Democratic Party. There, Kennedy worked for Charlie Manatt, his uncle Ted Kennedy's law school roommate.

Meanwhile, he had done a bit of acting, which was one of his passions (he had appeared in many plays while at Brown). He expressed interest in acting as a career, but his mother strongly disapproved of it, as an unsuitable profession. On August 4, 1985, Kennedy made his New York acting debut in front of an invitation-only audience at the Irish Theater on Manhattan's West Side. Executive Director of the Irish Arts Center, Nye Heron, said that Kennedy was "one of the best young actors I've seen in years". Kennedy's Director, Robin Saex, stated, "He has an earnestness that just shines through." Kennedy's largest acting role was playing a fictionalized version of himself in the season-eight episode of sitcom Murphy Brown, called "Altered States". In this episode, Kennedy visits Brown at her office, in order to promote a magazine he is publishing.

Kennedy had known Actress Daryl Hannah since their two families had vacationed together in St. Maarten in the early '80s. After meeting again at the wedding of his aunt Lee Radziwill in 1988, they dated for five and a half years, though their relationship was complicated by her feelings for singer Jackson Browne, with whom she had lived for a time.

From 1989, Kennedy headed Reaching Up, a nonprofit group which provided educational and other opportunities for workers who helped people with disabilities. william Ebenstein, executive Director of Reaching Up, said, "He was always concerned with the working poor, and his family always had an interest in helping them."

In 1989, Kennedy earned a J.D. degree from the New York University School of Law. He then failed the New York bar exam twice, before passing on his third try in July 1990. After failing the exam for a second time, Kennedy vowed that he would take it continuously until he was ninety-five years old or passed. If he had failed a third time, he would have been out as a prosecutor in the Manhattan district attorney's office, where he worked for the next four years. On August 29, 1991, Kennedy won his first case as a prosecutor.

In the summer of 1992, he worked as a Journalist and was commissioned by The New York Times to write an article about his kayaking expedition to the Åland Archipelago, where he saved one of his friends from the water when his kayak capsized. He then considered creating a magazine with his friend, public-relations magnate Michael J. Berman – a plan which his mother thought too risky. In his 2001 book The Day John Died, Christopher Andersen wrote that Jacqueline had also worried that her son would die in a plane crash, and asked longtime-companion Maurice Tempelsman "to do whatever it took to keep John from becoming a pilot".

Kennedy participated in his cousin Patrick J. Kennedy's campaign for a seat in the Rhode Island House of Representatives by visiting the district. He sat outside the polling booth and had his picture taken with "would-be" voters. The polaroid ploy worked so well in the campaign that Patrick J. Kennedy used it again in 1994.

In 1995, Kennedy and Michael Berman founded George, a glossy, politics-as-lifestyle and fashion monthly, with Kennedy controlling 50 percent of the shares. Kennedy officially launched the magazine at a news conference in Manhattan on September 8, and joked that he had not seen so many reporters in one place since he failed his first bar exam.

After his relationship with Daryl Hannah ended, Kennedy cohabitated with Carolyn Bessette, who worked in the fashion industry and was the youngest daughter of william J. Bessette and Ann Messina Freeman. They were engaged for a year, though Kennedy consistently denied reports of this. On September 21, 1996, they married in a private ceremony on Cumberland Island, Georgia, where his sister, Caroline, was matron of honor and his cousin Anthony Radziwill was best man.

By early 1997, Kennedy and Berman found themselves locked in a power struggle, which led to screaming matches, slammed doors, and even one physical altercation. Eventually Berman sold his share of the company, and Kennedy took on Berman's responsibilities himself. Though the magazine had already begun to decline in popularity before Berman left, his departure was followed by a rapid drop in sales.

Kennedy took flying lessons at the FLIGHT Safety Academy in Vero Beach, Florida. In April 1998, he received his pilot's license, which he had dreamed about since he was a child.

A memorial Service was held for Kennedy on July 23, 1999 at the Church of St. Thomas More, which was a parish that Kennedy had often attended with his mother and sister. The invitation-only Service was attended by hundreds of mourners, including President Bill Clinton, who presented the family with photo albums of John and Carolyn on their visit to the White House from the previous year.

David Pecker, CEO of Hachette Filipacchi Magazines, who were partners in George, said that this was because Kennedy refused to "take risks as an Editor, despite the fact that he was an extraordinary risk taker in other areas of his life." Pecker said, "He understood that the target audience for George was the eighteen-to-thirty-four-year-old demographic, yet he would routinely turn down interviews that would appeal to this age group, like Princess Diana or John Gotti Jr., to interview subjects like Dan Rostenkowski or Vo Nguyen Giap." Shortly before his death, Kennedy had been planning a series of online chats with the 2000 presidential candidates. Microsoft was to provide the Technology and pay for it while receiving advertising in George. After his death, the magazine was bought out by Hachette, but folded in early 2001.

In 2000, Reaching Up, the organization which Kennedy founded in 1989, joined with The City University of New York to establish the John F. Kennedy, Jr. Institute. On September 19, 2003, the ARCO Forum at Harvard University's Kennedy School of Government was renamed to the John F. Kennedy Jr. Forum of Public Affairs. An active participant in Forum events, Kennedy had also been a member of the IOP's Senior Advisory Committee for fifteen years. Kennedy's paternal uncle, Ted, said the renaming would symbolically link Kennedy and his father while his sister, Caroline, stated the renaming represented his love of discussing politics.