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Charlyn Marie Marshall was born January 21, 1972 in Atlanta, Georgia, the second child of Charlie Marshall, a blues musician and pianist, and Myra Lee Marshall (nee Russell). She has one older sister, Miranda "Mandy." Her parents divorced in 1979 and remarried shortly thereafter. Her mother remarried and had a son Lenny, and the family travelled around often because of her stepfather's profession.

In early 2000s, Marshall's live performances had become erratic and unpredictable, and The New Yorker suggested, "It is foolhardy to describe a Cat Power event as a concert," citing "rambling confessions" and "[talking] to a friend's baby from the stage." Marshall later attributed this period to a drinking problem, telling HARP magazine in 2006: "I didn't know I was messed up." Marshall has admitted abusing alcohol in the past; in a 2006 interview with The New York Times, she declared herself to be sober, which she defined as having had "seven drinks in seven months."  Following the cancellation of the arranged tour of the Greatest album in 2006, Marshall used the hiatus to recover from what she described as a "psychotic break" brought on by mental exhaustion and alcohol abuse, which had left her feeling suicidal. As part of her recovery, she was admitted to the psychiatric ward at Mount Sinai Medical Center & Miami Heart Institute but left after a week, stating: "being in there wasn't me." She later likened the experience to "a pit of hell." Marshall gave a first person account of her breakdown in an interview for the November 2006 issue of Spin.  In 2012, after the release of Sun, Marshall began having trouble breathing and was hospitalized multiple times, though doctors were unable to diagnose her. "I thought I was dying," she recounted. "They told me they were going to put me in a coma to save my lungs. My friend came to visit and told me I'd made the Billboard Top 10 and all I could think was: 'I don't want to die.'" Marshall was subsequently diagnosed with hereditary angioedema, an immune disorder that causes sporadic swelling of the face and throat. In September 2012, she stated she had been hospitalized due to the condition over eight times, which led her to cancel her European tour.
Cat Power