Coolidge is a graduate of Florida State University. After singing around Memphis (including a stint singing jingles), she was discovered by Delaney & Bonnie, who took her to Los Angeles where, besides her work with Delaney & Bonnie, she became a popular background singer on many other people's albums. She sang for Leon Russell, Joe Cocker, Harry Chapin, Bob Dylan, Jimi Hendrix, Eric Clapton, Dave Mason, Graham Nash, and Stephen Stills. She was featured in Joe Cocker's Mad Dogs and Englishmen tour and album, singing Russell's and Bonnie Bramlett's song "Superstar." She became known as "The Delta Lady" and inspired Russell to write a song of the same name for her.
In November 1970, she met Kris Kristofferson at the Los Angeles airport when they were both catching the same flight to Tennessee. He got off in Memphis with her, rather than continue to his intended destination in Nashville. The two married in 1973 and recorded several duet albums, which sold well and earned the duo a Grammy Award for Best Country Performance by a Duo or Group with Vocal in 1974 for "From the Bottle to the Bottom", and in 1976 for "Lover Please".
Coolidge's greatest success on the pop charts came during 1977–78 with four consecutive top 25 hits, remakes of Jackie Wilson's "(Your Love Keeps Lifting Me) Higher and Higher", Boz Scaggs' "We're All Alone", The Temptations' "The Way You Do The Things You Do", and Marcia Hines' "You".
Coolidge also was among the first hosts on VH1, a U.S. cable network. In 2006, she recorded a standards album, And So Is Love.
In the recording of the original hit "Layla" by Eric Clapton's band Derek and the Dominos in 1970, Clapton returned to the studio where he heard the band's drummer Jim Gordon playing a piano piece he had allegedly composed himself separately. Clapton, impressed by the piece, convinced Gordon to allow it to be used as part of the song in the coda section. Though only Gordon has been officially credited with this part, the band's keyboardist Bobby Whitlock claims, "Jim took that piano melody from his ex-girlfriend, Rita Coolidge. I know because in the Delaney & Bonnie days, I lived in John Garfield's old house in the Hollywood Hills and there was a guest house with an upright piano in it. Rita and Jim were up there in the guest house and invited me to join in on writing this song with them called "Time". Her sister Priscilla wound up recording it with her husband, Booker T. Jones (of Booker T. & the M.G.'s). Jim took the melody from Rita's song and didn't give her credit for writing it. Her boyfriend ripped her off". "Time" ended up on the 1973 album Chronicles by Booker T. and Priscilla.