In 1961, his record "You Can't Sit Down" by the Philip Upchurch Combo,[2] sold over one million copies and was awarded a gold disc.

Upchurch was part of a group called The Soulful Strings during the 1960s, prior to working with the Rotary Connection on Chess's Cadet label.

In the 1970s, he worked with Donny Hathaway, Harvey Mason, Ramsey Lewis, Quincy Jones and led his own quartet with Tennyson Stephens.

[6] In the mid-1970s and 1980s, he performed with George Benson,[5] Mose Allison, Gary Burton, Lenny Breau,[7] Joe Williams, Chaka Khan, Natalie Cole, Carmen McRae, Cat Stevens, David Sanborn, and Michael Jackson.

With Mose Allison With Anita Baker With George Benson With Oscar Brown Jr. With Peabo Bryson and Natalie Cole With Dee Clark With Natalie Cole With Bob Dylan With Sheena Easton With Stan Getz With Dizzy Gillespie With Donny Hathaway With Red Holloway With Howlin' Wolf With Michael Jackson With Dr. John With Chaka Khan With Hubert Laws With Ramsey Lewis With Jack McDuff With Carmen McRae With Jimmy Reed With Minnie Riperton With Rotary Connection With Ben Sidran With Jimmy Smith With Muddy Waters