Kooper’s first professional work was as a 14-year-old guitarist in the Royal Teens, best known for their 1958 ABC Records novelty 12-bar blues riff, “Short Shorts” (although Kooper did not play on the recording). In 1960, he teamed up with songwriters Bob Brass and Irwin Levine to write and record demos for Sea-Lark Music Publishing. The trio’s biggest hits were “This Diamond Ring”, recorded by Gary Lewis and the Playboys, and “I Must Be Seeing Things”, recorded by Gene Pitney (both 1965). When he was 21, Kooper moved to Manhattan’s Greenwich Village, then teeming with artists, writers, and musicians.

He performed with Bob Dylan in concert in 1965, including playing Hammond organ with Dylan at the Newport Folk Festival, and in the recording studio in 1965 and 1966. Kooper also played the Hammond organ riffs on Dylan’s “Like a Rolling Stone”. It was in those recording sessions that Kooper met and befriended Mike Bloomfield, whose guitar playing he admired. He worked extensively with Bloomfield for several years. Kooper played organ once again with Dylan during his 1981 world tour.

Kooper joined the Blues Project as their keyboardist in 1965; he left the band shortly before their gig at the Monterey Pop Festival in 1967, although he did play a solo set at the famous festival, as evidenced by bootlegs of the event. He formed Blood, Sweat & Tears in 1967, leaving due to creative differences in 1968, after the release of the group’s first album, Child Is Father to the Man. He recorded Super Session with Bloomfield and Stills in 1968, and in 1969 he collaborated with 15-year-old guitarist Shuggie Otis on the album Kooper Session. In 1975 he produced the debut album by the Tubes.

After moving to Atlanta in 1972, he discovered the band Lynyrd Skynyrd, and produced and performed on their first three albums, including the singles “Sweet Home Alabama” and “Free Bird”. In 1972 he rejoined the Blues Project at a charity concert promoted by Bruce Blakeman at Valley Stream Central High School.

In May 2001, Kooper was awarded an Honorary Doctorate of Music from Berklee College of Music. Kooper is retired from teaching songwriting and recording production at Berklee College of Music, in Boston, and plays weekend concerts with his bands the ReKooperators and the Funky Faculty. In 2008, he participated in the production of the album Psalngs, the debut release of Canadian musician John Lefebvre.

In 2005, Martin Scorsese produced a documentary titled No Direction Home: Bob Dylan for the PBS American Masters Series in which Kooper’s contributions are recognized.

Kooper was inducted into the Musicians Hall of Fame and Museum, in Nashville, in 2008.

Kooper published a memoir, Backstage Passes: Rock ‘n’ Roll Life in the Sixties (1977), which was revised and published as Backstage Passes and Backstabbing Bastards: Memoirs of a Rock ‘n’ Roll Survivor (1998). The revised edition includes indictments of “manipulators” in the music industry, including his one-time business manager, Stan Polley. An updated edition, including supplementary material, was published by Backbeat Books in 2008.