Travolta, the youngest of six children, was born and raised in Englewood, New Jersey, an inner-ring suburb of Bergen County, New Jersey. His father, Salvatore Travolta (November 1912 – May 1995), was a semi-professional American football player turned tire salesman and partner in a tire company. His mother, Helen Cecilia (née Burke; January 18, 1912 – December 1978), was an Actress and singer who had appeared in The Sunshine Sisters, a radio vocal group, and acted and directed before becoming a high school drama and English Teacher. His siblings, Joey, Ellen, Ann, Margaret, and Sam Travolta, have all acted. His father was a second-generation Italian American (with roots in Godrano, Sicily) and his mother was Irish American; he grew up in an Irish-American neighborhood and has said that his household was predominantly Irish in culture. He was raised Roman Catholic, but converted to Scientology in 1975. Travolta attended Dwight Morrow High School, but dropped out as a junior at age 17 in 1971.

Travolta's first California-filmed television role was as a fall victim in Emergency! (S2E2), in September 1972, but his first significant movie role was as Billy Nolan, a bully who was goaded into playing a prank on Sissy Spacek's character in the horror film Carrie (1976). Around the same time, he landed his star-making role as Vinnie Barbarino in the TV sitcom Welcome Back, Kotter (1975–1979), in which his sister, Ellen, also occasionally appeared (as Arnold Horshack's mother). The show aired on ABC.

Travolta has been a practitioner of Scientology since 1975 when he was given the book Dianetics while filming the movie The Devil's Rain in Durango, Mexico. After the 2010 Haiti earthquake, joining other celebrities in helping with the relief efforts, Travolta flew his Boeing 707 full of supplies, doctors, and Scientologist Volunteer Ministers into the disaster area.

Travolta had a hit single entitled "Let Her In," peaking at number 10 on the Billboard Hot 100 chart in July 1976. In the next few years, he starred in The Boy in the Plastic Bubble and two of his most noted screen roles: Tony Manero in Saturday Night Fever (1977) and as Danny Zuko in Grease (1978). The films were among the most commercially successful pictures of the decade and catapulted Travolta to international stardom. Saturday Night Fever earned him an Academy Award nomination for Best Actor, making him, at age 24, one of the youngest performers ever nominated for the Best Actor Oscar. His mother and his sister Ann appeared in minor roles in Saturday Night Fever and his sister Ellen appeared as a waitress in Grease. Travolta performed several of the songs on the Grease Soundtrack album. In 1980, Travolta inspired a nationwide country music craze that followed on the heels of his hit film, Urban Cowboy, in which he starred with Debra Winger.

After Urban Cowboy, Travolta starred in a series of commercial and critical failures that sidelined his acting career. These included Two of a Kind (1983), a romantic comedy reteaming him with Olivia Newton-John, and Perfect (1985), co-starring Jamie Lee Curtis. He also starred in Staying Alive, the 1983 sequel to Saturday Night Fever, for which he trained rigorously and lost twenty pounds; the film was a financial success grossing over $84,000,000 though it too was scorned by critics.

In 1989, Travolta starred with Kirstie Alley in Look Who's Talking, which grossed $297 million making it his most successful film since Grease. Next came Look Who's Talking Too (1990) and Look Who's Talking Now (1993) but it was not until he played Vincent Vega in Quentin Tarantino's hit Pulp Fiction (1994), for which he received an Academy Award nomination, that his career revived. The movie shifted him back onto the A-list, and he was inundated with offers. Notable roles following Pulp Fiction include a movie-buff loan shark in Get Shorty (1995), an FBI agent and terrorist in Face/Off (1997), a desperate attorney in A Civil Action (1998), a Bill Clinton-esque presidential candidate in Primary Colors (1998), and a military investigator in The General's Daughter (1999).

In May 1991, Time magazine published a cover story entitled "The Thriving Cult of Greed and Power". In the article, former Church of Scientology Executive Director william Franks alleged that Travolta was wary of leaving the faith because he feared the Church would publish detailed revelations of his private life, to include homosexual behavior. These claims were reiterated by Franks and other Scientology defectors in Lawrence Wright's 2013 book Going Clear: Scientology, Hollywood, and the Prison of Belief, and former Church official Marty Rathbun claimed that he worked with Travolta's attorneys several times to keep allegations about Travolta's homosexuality out of the press and resolve lawsuits against the star.

On November 24, 1992, Travolta was piloting his Gulfstream N728T at night above a solid undercast, when he experienced a total electrical system failure while flying under instrument FLIGHT rules into Ronald Reagan Washington National Airport. During the emergency landing, he almost had a mid-air collision with a USAir Boeing 727, an event attributed to a risky decision by an air traffic controller.

Throughout the 2000s, Travolta remained busy as an actor, starring in many films including Swordfish (2001), Ladder 49 (2004), Be Cool (2005), Wild Hogs (2007), the animated film Bolt (2008), in which Travolta voiced the title character, The Taking of Pelham 123 and Old Dogs (both 2009).

Travolta was inducted into the Living Legends of Aviation in 2007 and acts as the award show's official ambassador.

In 2009, Travolta's son, Jett, died at age 16 while on a Christmas vacation in the Bahamas. A Bahamian death certificate was issued, attributing the cause of death to a seizure. Jett, who had a troubled history of seizures, reportedly suffered from Kawasaki disease at the age of two. Travolta confirmed speculation that his son had autism and suffered regular seizures and immediately made his public statements while giving testimony after a multimillion-dollar extortion plot against him in connection to his son's death. After a mistrial, Travolta dropped the charges and has credited his immediate family and Scientology with helping him survive the death of his son and in moving forward with his film career. In memory of his son, Travolta founded the Jett Travolta Foundation, a non-profit organization to help children with special needs. It has contributed to organizations such as the Oprah Winfrey Leadership Academy, The Institutes for the Achievement of Human Potential, and the Simon Wiesenthal Center

On September 13, 2010, during the first episode of the final season of her talk show, Oprah Winfrey announced that she would be taking her entire studio audience on an 8-day expenses-paid trip to Australia, with Travolta serving as pilot for the trip. He had helped Winfrey plan the trip for more than a year.

A judge ruled to dismiss a defamation lawsuit against Travolta and his attorney Marty Singer by Writer Robert Randolph. Los Angeles Superior Court Judge Malcolm Mackey dismissed the case on September 27, 2012, because he found that a letter, written by Singer in response to allegations in a book by Randolph, had free speech protection.

Travolta was nominated for the Academy Award for Best Actor for performances in Saturday Night Fever and Pulp Fiction. He won his only Golden Globe Award for Best Actor in a Motion Picture – Musical or Comedy for his performance in Get Shorty and has received a total of six nominations, the most recent being in 2008. In 2014, he received the IIFA Award for Outstanding Achievement in International Cinema. In 2016, Travolta received his first Primetime Emmy Award, as a Producer of the first season of the anthology series American Crime Story, subtitled The People v. O. J. Simpson. He also received an additional Emmy nomination and a Golden Globe nomination for his portrayal of Lawyer Robert Shapiro in the series.

In September 2014, Travolta denied claims made in January 2014 by his former pilot, Douglas Gotterba, that they had shared a sexual relationship while working for Travolta's aircraft company, Alto, for six years before leaving voluntarily in 1987.

Travolta is a private pilot and owns four aircraft. This excludes the ex-Qantas Boeing 707-138B (Ex-VH-EBM) that he owned. In 2017, the plane was donated to the Historical Aircraft Restoration Society (HARS) near Wollongong, Australia. Travolta has expressed interest in being among the crew to fly it to Illawarra Regional Airport, where HARS is based. The plane will be repaired to ensure safe flying condition. The 707 aircraft bears an old livery of Qantas, and Travolta acted as an official goodwill ambassador for the airline wherever he flew. Travolta named his 707 "Jett Clipper Ella," in honour of his children. The "Clipper" in the name represents that Pan Am used that word in the names of their aircraft.