She has two older sisters, Kathy and Karen, and one younger brother, Steve. Crow began playing piano at age six. She graduated from Kennett High School in 1980 and the University of Missouri at Columbia in 1984, where she majored in music education. During college, she spent her weekends performing with a local band, Cashmere.

After college, Crow worked as a music teacher in an elementary school in St. Louis before moving to Los Angeles in 1986. She began recording jingles for advertising clients, including McDonald's, and worked as a back-up singer. In 1987-88 she sang on Michael Jackson's "Bad" world tour. She later sang back-up for Sting, Rod Stewart and Don Henley. In 1991 Crow recorded an album for A&M Records which she shelved because it sounded too "slick." She began playing with the band The Tuesday Music Club, comprised of Bill Bottrell, David Baerwald, David Ricketts, and Sheryl's then-boyfriend Kevin Gilbert. In 1993 the group released the multi-platinum album Tuesday Night Music Club which included the smash hit, "All I Wanna Do."

In 1995, she won three Grammy Awards for Best New Artist, Record of the Year (for "All I Want to Do"), and Best Female Pop Vocal Performance for Tuesday Music Club. She also performed a MTV Unplugged session in 1995. Crow released the album Sheryl Crow in 1996, winning two Grammy Awards for Best Rock Album and Best Female Rock Vocal Performance. She spent much of 1997-98 on tour, playing select dates on the Rolling Stones' Bridges to Babylon tour and performing at the 1998 Lilith Fair concerts. She released her third album The Globe Sessions in the fall of 1998, which won a Grammy for Best Rock Album. During 1999, Crow performed in Europe and toured with Lilith Fair throughout the United States. At the Grammy Awards in February 2000, Crow won for Best Female Rock Vocal Performance, for her rendition of the Guns 'n Roses hit "Sweet Child o'Mine."