He began his career as a jazz musician, and writing commercials for radio and television. In 1955 the little-known LP recording of Jean Shepherd Into the Unknown with Jazz Music was produced with Leigh writing the music for the jazz interludes between radio broadcaster Jean Shepherd's improvisations. In 1965 Leigh teamed with lyricist Joe Darion and writer Dale Wasserman to write a musical based on Wasserman's 1959 television play, I, Don Quixote. The resulting show, the musical Man of La Mancha opened on Broadway in 1965 and in its original engagement ran for 2,328 performances.
Leigh's next show was Chu Chem. This show followed Man of La Mancha by exactly one year, but closed on the road. Produced by Leigh, it opened on Broadway in 1989 for 68 performances.
Cry for Us All, based on the play, Hogan's Goat, opened on Broadway in 1970 but ran for 9 performances. Leigh was the producer as well as composer. His next musical was Home Sweet Homer, starring Yul Brynner, which opened on Broadway officially in January 1976 but closed after 1 performance. He produced as well as was the composer for Saravà which ran for 101 performances in 1979. Leigh both produced and directed the 1985 revival of The King and I starring Yul Brynner. Lee Adams asked Leigh to collaborate on a musical, entitled Mike, about producer Mike Todd, but it closed during its pre-Broadway tryout in 1988. After renaming it Ain't Broadway Grand!, the show made it to Broadway, but closed after 25 performances in 1993.
Leigh also composed the jingle: "Nobody Doesn't Like Sara Lee". He established Music Makers, Inc., in 1957 as a radio and television commercial production house and was its creative director. He also composed the instrumental music for the ABC Color Logo (1962-65) and the Benson and Hedges theme "The Dis-Advantages Of You", which reached the Top 40 for The Brass Ring, 1967.
In 1977, Leigh and others at the Yale School of Music established the Keith Wilson scholarship, to be awarded "to an outstanding major in wind instrument playing."
A building in The School of Music at Yale University was named "Abby and Mitch Leigh Hall" in 2001.
Leigh endowed a chair in jazz at Yale University, the Willie Ruff Chair in Jazz, in 2006.
Leigh died at Manhattan on March 16, 2014 from natural causes at the age of 86.
He received the Contemporary Classics Award from the Songwriter’s Hall of Fame for "The Impossible Dream."
- YAM March 2001 - Who's Been Blue
- Suskin, Steven."Mitch Leigh's Cry For Us All Comes to CD, Plus Kitty's Kisses", playbill.com, October 25, 2009
-  Archived October 9, 2011, at the Wayback Machine.
- Weber, Bruce (2011-05-02). "Sidney Michaels, 83, Author Of Hit Broadway Shows - Obituary (Obit); Biography - NYTimes.com". New York Times. Retrieved 2013-01-05.
- "Advertising Jingle Music Folio Books", classicthemes.com, accessed February 9, 2010
- "Composer Mitch Leigh Endows Chair in Jazz at Yale", opa.yale.edu, September 12, 2006
- "Yale School of Music Names Building in Honor of Mitch and Abby Leigh", opa.yale.edu, September 7, 2001