Phillips, who was born in Glendale, California, began her musical career as a vocalist in the early 1980s, singing background parts for Mark Heard, Randy Stonehill and other artists. After a short time, Phillips was signed to Myrrh Records where she went on to record four pop albums, Beyond Saturday Night, Dancing with Danger, Black and White in a Grey World and, finally, The Turning, which teamed her with producer and future husband, producer T-Bone Burnett.
Although Phillips earned the nickname "Sam" as a child, she didn't start using it professionally until 1988 when she left Myrrh Records and signed with Virgin Records. Soon after, she released The Indescribable Wow, which featured the orchestrations of Brian Wilson lyricist, Van Dyke Parks. Cruel Inventions, which was released in 1991, included a guest appearance from close friend, Elvis Costello. 1994's Martinis and Bikinis, was widely praised by music critics and was even nominated for a Grammy Award, which was Phillips' first nomination. That year also gave Phillips a chance to write a song with Brian Wilson, which would appear on Rob Wasserman's Trios album, performed by Carnie Wilson.
In 1996, Phillips released Omnipop (It's Only A Flesh Wound Lambchop), which featured a song cowritten by Phillips and REM. Omnipop, which was more experimental musically, ended up being her worst selling album to date.
In 2001, she released a stripped down acoustic album called Fan Dance, which featured some of the best songwriting of Phillips' career. Van Dyke Parks contributed beautiful string arrangements for a track or two. Phillips also began writing music for the television series, Gilmore Girls.