Post's first credited work in music was cutting demos using two singing sisters, Terry and Carol Fischer. With Sally Gordon, they went on to become The Murmaids. Their first single, "Popsicles and Icicles" (written by David Gates), was a #3 hit song in January 1964.
Post also worked with Kenny Rogers and produced the first three albums he recorded with his country/rock group the First Edition (between 1967 and 1969). Post also produced Dolly Parton's hit album 9 to 5 and Odd Jobs in 1981. Much later, in 1997, he produced Van Halen's Van Halen III album.
He won his first Grammy at age 23 for Best Instrumental Arrangement on Mason Williams' "Classical Gas", a #2 hit song in 1968. He is also credited as the Producer for Williams' LP that included this song, The Mason Williams Phonograph Record.
One of his first jobs in television started when he was 24, as the musical Director on The Andy Williams Show. Another early job was writing the theme music for the short-lived detective series Toma in 1973, but his big breakthrough (together with co-composer Pete Carpenter) came in the following year with his theme song for The Rockford Files, another series by Producer Stephen J. Cannell. The theme also got cross-over Top 40 radio airplay and earned a second Grammy for Post.
Post subsequently won Grammys for Best Instrumental Composition for the themes of the television shows Hill Street Blues in 1981 and L.A. Law in 1988 as well as another Grammy in 1981 for Best Instrumental Performance for the Hill Street Blues theme, which also reached number 10 in the U.S.
In 1994, Post released a CD, called Inventions from the Blue Line. The CD contained several of his well-known themes, featuring NYPD Blue and also including Law & Order, Silk Stalkings and Renegade. In the liner notes, he discussed his late father, Sam Postil, and the admiration for law enforcement officers that Sam instilled in Mike. He also referred to police in the traditional nickname of "blues", as in The Thin Blue Line (referring to the police in general and to police camaraderie). One of the tracks is called "The Blue Line", which Post calls "the comradery theme".
The Pete Townshend song "Mike Post Theme", which alludes to the ubiquity of Post's work in television theme music, appears on The Who's 2006 album, Endless Wire.
In 2014, Post composed the score for the fake TV plot Caged Heat in the Marvel One-Shot All Hail the King for Marvel Studios.