In 1962, he had a starring role in I Can Get It for You Wholesale, which ran for 300 performances and where he met future wife Barbra Streisand. Following that, he landed prominent roles in Drat! The Cat! (1965) and in Little Murders (1971). He was also cast A Way of Life by Murray Schisgal but walked out prior to the play making it to Broadway.

Following his film debut in the comedy Quick, Let’s Get Married (1964), Gould’s next film appearance was in William Friedkin’s The Night They Raided Minsky’s (1968). In January 1969, Gould announced he had formed his own film production company with Jack Brodsky, Brodsky-Gould Productions. The company would make two films: The Assistant, based on a novel by Bernard Malamud, and Little Murders. (The Assistant was never produced.) In April 1970, Brodsky and Gould announced plans to make The Dick, from the novel by Bruce Jay Friedman, but it was never made.

In March 1969, Gould signed a non-exclusive, four-picture contract with 20th Century Fox, the first of which was to be M*A*S*H and the second Move.

He reached a new level of prominence that year, playing one of the four leads in Paul Mazursky’s zeitgeisty social comedy Bob & Carol & Ted & Alice, released in September 1969. He earned a nomination for the Academy Award for Best Supporting Actor for his performance. “I’m the hottest thing in Hollywood right now,” he said in October 1969.

Following his starring role in the stage version, Gould bought the rights for Little Murders with an eye to producing and reprising his lead role in a film adaptation. Directed by Alan Arkin, and released in 1971, it was another commercial disappointment, but has since earned a cult following.

He joined the ensemble cast of A Bridge Too Far in 1977 and played the lead in boxing kangaroo comedy Matilda the year after.

During this period Gould hosted Saturday Night Live six times, his final time being the first episode of the disastrous Jean Doumanian season (season 6) in November 1980, where he was shocked to find that the original cast and producer Lorne Michaels were gone and had been replaced. Although he never hosted SNL again, he did appear in a season 16 (1990–1991) episode hosted by Tom Hanks where Hanks is welcomed into the Five-Timers club, a society for celebrities who have hosted the show five times.

He starred in the much-maligned remake of The Lady Vanishes (1979). Another flop came with Falling in Love Again (1980), co-starring Susannah York. Gould also made two films for Disney, The Last Flight of Noah’s Ark (1980) and The Devil and Max Devlin (1982). He made his return to Broadway with The Guys in the Truck in 1983.

He became known to a new generation of viewers thanks to a recurring role as Jack Geller, the father of Courteney Cox and David Schwimmer’s characters Monica and Ross, on the NBC sitcom Friends, first appearing in 1994 and in twenty total episodes over the course of the show’s run. Around the same time he took a more dramatic role, as the boyfriend of the protagonist’s mother, in the controversial drama American History X (1998). He co-starred in Steven Soderbergh’s Ocean’s Eleven, a 2001 remake of the classic Rat Pack caper film. He reprised the role for its sequels, Ocean’s Twelve in 2004 and Ocean’s Thirteen in 2007, as well as its spin-off Ocean’s 8 in 2018. He had another supporting turn in Soderbergh’s Contagion (2011), followed by Ruby Sparks in 2012. More recently, he co-starred with Jemaine Clement in the human comedy Humor Me (2017).

In 2005 he guest starred in a feature-length episode of the UK TV series Poirot, subsequently appearing in similar one-off or small roles in television series including Law & Order and CSI, and a more significant role in Showtime’s Ray Donovan from 2013 to 2016. He has loaned his voice to several animated series, including the Disney Channel animated series Kim Possible, and the 2006 video game Scarface: The World Is Yours.

Gould currently serves on the Screen Actors Guild National Board of Directors. He became one of the many celebrity producers of The 1 Second Film collaboration in June 2009 and is known for his association to charitable causes such as Save Ellis Island.