In 1965, Tune made his Broadway debut as a performer in the musicalBaker Street. His first Broadway directing and choreography credits were for the original production of The Best Little Whorehouse in Texas in 1978. He has gone on to direct and/or choreograph eight Broadway musicals. He directed a new musical titled Turn of the Century, which premiered at the Goodman Theatre in Chicago on September 19, 2008 and closed on November 2, 2008.
Tune is the only person to win Tony Awards in the same categories (Best Choreography and Best Direction of a Musical) in consecutive years (1990 and 1991), and the first to win in four categories. He has won nine Tony Awards.
On television, Tune was a recurring guest star and assistant choreographer from 1969-70 on The Dean Martin Show and its summer replacement series, Dean Martin Presents The Golddiggers.
Tune's film credits include Ambrose in Hello, Dolly! (1969), and The Boy Friend with Twiggy (1971). Tune released his first record album, Slow Dancing, in 1997 on the RCA label, featuring a collection of his favorite romantic ballads.
Tune staged an elaborate musical entitled Paparazzi for the Holland America Line cruise ship the Oosterdam in 2003. He works often with The Manhattan Rhythm Kings, for example touring in a Big Band revue entitled Song and Dance Man and White Tie and Tails (2002).
Tune has been performing in his musical revue, Steps in Time: A Broadway Biography in Song and Dance, in Boston in April 2008 and continuing in various venues from Bethesda, Maryland in January 2009 to California in February 2009.
The Tommy Tune Awards, presented annually by Theatre Under The Stars (TUTS) honor excellence in high school musical theatre in Houston. The current home of the Tommy Tune Awards is the Hobby Center for the Performing Arts in Houston, Texas.
When not performing, he used to run an art gallery in Tribeca that featured his own work.As of 2014 it is no longer open.  In Tune's 1997 memoirFootnotes, he writes about what drives him as a performer, choreographer and director, offers stories about being openly gay in the world of theatre, his partners David Wolfe and Michael Stuart, about his days with Twiggy in My One and Only and meeting and working with his many idols.
Before leaving Texas in the 1960s for a Broadway career in New York, Tune worked with Mary Highsmith, mother of crime novelist Patricia Highsmith, at the Point Summer Theatre. In a letter to her daughter, Highsmith referred to Tune as her "adopted boy" whom she called "Romano." Tune later praised Highsmith for helping him develop his talents: "She was an opening for me; she opened a little bit of my tight fabric so that I might peer through."