Welch was born in Manhattan and was adopted when she was three days old. She moved to Los Angeles at the age of four. On her eighth birthday she wished for and got a guitar and lessons, and learned soon to play the guitar. Studying at the University of California, Santa Cruz,[3] Welch discovered bluegrass music through the "mountain soul" stylings of The Stanley Brothers.[4] After a short stint playing bass in a local camp band called Söfa, Welch moved to Boston and studied at the Berklee College of Music.

In Boston, Welch met and began dating David Rawlings, who would become her long-time musical partner. In 1992, they moved to Nashville and began building a career. In Nashville, she met T-Bone Burnett,[5] producer to such artists as Los Lobos, Sam Phillips, Bodeans, Counting Crows, and Elvis Costello. In 1996, Welch released her first album, Revival, which was nominated for a Grammy for Best Contemporary Folk Album in 1997.[2] Since then, she has recorded other albums and collaborated on the songs "Didn't Leave Nobody But the Baby" and "I'll Fly Away" on the Grammy-winning soundtrack of the Coen Brothers hit film O Brother, Where Art Thou?.[6] Welch also had a cameo in the film, as a woman in a record store trying to obtain a copy of the Soggy Bottom Boys' recording of "Man of Constant Sorrow".

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