Coolidge was born in Lafayette, Tennessee. Between 1969 and 1979, she was married to Booker T. Jones, who produced Coolidge's first solo album, 1970's Gypsy Queen. Then the pair collaborated as a duo on three albums: 1971's Booker T. & Priscilla; 1972's Home Grown; and 1973's Chronicles, which included the song "Time", written by her sister Rita, which was allegedly "borrowed" by drummer Jim Gordon (formerly of Eric Clapton's band Derek and the Dominos and Rita's former boyfriend) and became the famous instrumental piano coda at the end of "Layla"). Jones produced Priscilla's final solo album, Flying, in 1979; their marriage ended that year.

In 1981 Coolidge married TV journalist/broadcaster/reporter Ed Bradley. Her marriage to Bradley ended in divorce, and she later married Michael Seibert.

Seibert and Coolidge were found dead in their home in Thousand Oaks, California. On October 2, 2014,in what the local police later described a murder–suicide, after the couple were heard by neighbors in a heated argument. Seibert shot Priscilla in the head, and soon after killed himself.