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Cruise's first film role came in 1981, when he had a small role in Endless Love, a drama/romance film starring Brooke Shields. Later that same year he had a more substantial role in the film Taps, appearing alongside George C. Scott, Timothy Hutton and Sean Penn. The film about military cadets was moderately successful. In 1983, he was one of many teenaged stars to appear in Francis Ford Coppola's The Outsiders. The cast for this film included Rob Lowe, Matt Dillon, Patrick Swayze, and Ralph Macchio, two of which were part of the Brat Pack. That same year Cruise appeared in the teen comedy Losin' It. Cruise's breakthrough came after Risky Business was released, which helped to propel Cruise to stardom. One sequence in the film, featuring Cruise lip-syncing Bob Seger's "Old Time Rock and Roll" in his underwear, has become an iconic moment in 1980s film. The film has been described as "A Generation-X classic, and a career-maker for Tom Cruise". A fourth film that was released in 1983 was the high-school football drama, All the Right Moves. Cruise's next film was the 1985 fantasy film Legend directed by Ridley Scott.

Cruise was then selected as the first choice by producers Jerry Bruckheimer and Don Simpson for an upcoming American fighter pilot film. Cruise at first apparently turned down the project, but helped to alter the script he was given and developed the film. After being taken for a flight with the Blue Angels, Cruise changed his mind and signed on with the project. The project was titled Top Gun and opened in May 1986, becoming the highest grossing film of the year, taking in US$354 million in worldwide figures. Also in 1986, he starred in Martin Scorsese's The Color of Money along with Paul Newman, which earned Paul a Best Actor Academy Award. In 1988, he starred in the lighthearted drama Cocktail, which received mixed reviews and Cruise received his first nomination for a Razzie award in 1989. Later that year, Rain Man was released, which also starred Dustin Hoffman and was directed by Barry Levinson. The film was praised by critics and was nominated for eight Academy Awards, and won four, including Best Picture and Best Actor.

Cruise was welcomed with similar success the following year when he received Academy Award nominations for Oliver Stone's Born on the Fourth of July, which was based on the best selling autobiography of parapalegic veteran and anti-war activist Ron Kovic. In 1990, Cruise starred as hot-shot racecar driver "Cole Trickle" in Tony Scott's Days of Thunder. Cruise's next film was Ron Howard's Far and Away where he again was starring with Nicole Kidman. After Days of Thunder he starred in the military thriller A Few Good Men with Jack Nicholson and Demi Moore. This film was very well received and earned Cruise a Golden Globe and MTV nominations. The following year he starred in Sydney Pollack's The Firm along with Gene Hackman and Ed Harris. It was based on the best selling novel by John Grisham, and won Favorite Dramatic Motion Picture at the People's Choice Awards.

In 1994, Cruise starred along with Brad Pitt, Antonio Banderas and Christian Slater in Neil Jordan's Interview with the Vampire, a gothic drama/horror film that was based on Anne Rice's best-selling novel. The film was well received, although Rice was outspoken in her criticism of Cruise having been cast in the film, as River Phoenix was her first choice. In 1996, Cruise starred in (as well as produced) Brian de Palma's Mission: Impossible. The film, a remake of the 1960s TV series, grossed US$456 million worldwide, making it the third highest grossing film that year. That same year he played the title role in the comedy-drama Jerry Maguire. The film earned him an Academy Award Best Actor nomination as well as winning co-star Cuba Gooding, Jr. an Academy Award; the film was nominated for five Academy Awards in total. The film also included the catchphrase "Show Me the Money!" which became part of popular culture. In 1999 he starred in the erotic thriller Eyes Wide Shut which took two years to complete and was director Stanley Kubrick's last film. It was also the last film in which he starred alongside then spouse Nicole Kidman. But the film, which had a straightforward description of sex and a recondite story-telling style, raised great controversies. Cruise also played a misogynistic male guru in Magnolia (1999), which netted him a Best Supporting Actor Oscar nomination. He was originally intended to play as Jericho Cane in the action horror film End of Days before Arnold Schwarzenegger assumed the lead role.

In 2000, Cruise returned as Ethan Hunt in the second installment of the Mission Impossible films, releasing Mission: Impossible II. The film was directed by Hong Kong director John Woo and branded with his Gun fu Style, and it continued the series' blockbuster success at the box office, taking in almost US$546 M in worldwide figures, like its predecessor, being the third highest grossing film of the year. The following year Cruise starred in the remake of the 1997 film Abre Los Ojos, Vanilla Sky. In 2002, Cruise starred in the dystopian science fiction thriller, Minority Report which was directed by Steven Spielberg and based on the science fiction short story by Philip K. Dick; and the following year, he was in Edward Zwick's historical drama The Last Samurai.

In the 2004 Michael Mann's crime-thriller film Collateral, Cruise took a turn against his generic "good guy" role by playing the role of a sociopathic hitman. In 2005, Cruise worked again with Steven Spielberg in War of the Worlds, which became the fourth highest grossing movie of the year with US$591.4 M worldwide. The film also earned three Razzie nominations including one for Cruise. In 2006, he reprised his role as Ethan Hunt in the third installment of the Mission Impossible film series, Mission: Impossible III. Although it was more positively received by critics than its predecessor, it disappointed at the box office, grossing nearly $150M less worldwide. He appeared in the 2007 drama Lions for Lambs, which bombed, and had a comedic supporting role in the 2008 comedy Tropic Thunder. Cruise's latest starring role is in the historical thriller Valkyrie, released on December 25, 2008 to mixed reviews.