Welch was born in 1967 in Manhattan and grew up in West Los Angeles, where her parents wrote material for the comedy program The Carol Burnett Show. It was as a child that she became fascinated by bluegrass and early country music, in particular the work of the Stanley Brothers, the Delmore Brothers, and the Carter Family.

In the early '90s, Welch attended the Berklee School of Music in Boston, Massachusetts, where she began performing her own material, as well as traditional country and bluegrass songs, as part of a duo with fellow student David Rawlings. After honing their skills in local open mike showcases, the duo began performing regularly throughout the country. While opening for Peter Rowan in Nashville, they were spotted by musician and producer T-Bone Burnett, who helped Welch and Rawlings land a record deal. With Burnett producing, they cut 1996's starkly beautiful Revival, an album split between bare-bones duo performances -- some even recorded in mono to capture a bygone sound -- and more full-bodied cuts featuring legendary sessionmen like guitarist James Burton, upright bassist Roy Huskey, Jr., and drummers Buddy Harmon and Jim Keltner.

Her sophomore album, Hell Among the Yearlings, followed in 1998. The years following her second release found Welch involved in several soundtracks (O Brother, Where Art Thou?, Songcatcher), tribute albums (Songs of Dwight Yoakam: Will Sing for Food, Return of the Grievous Angel: A Tribute to Gram Parsons), and guest spots on other artists' albums (Ryan Adams' Heartbreaker, Mark Knopfler's Sailing to Philadelphia). Following the success of O Brother, Welch and Rawlings found themselves in the center of a traditional American folk revival and released their third album, Time (The Revelator), in mid-2001. Steady touring, guest appearances, and the release of a DVD (The Revelator Collection) kept the pair busy, but in 2003 they found time to record Soul Journey, their second release on their own Acony Records label. Rawlings cut his first solo album, A Friend of Mine, though Welch sang harmony all over it. It was issued in 2009. Welch didn't release another album under her own name again until 2011, when she and Rawlings released The Harrow & The Harvest on Acony. She and Rawlings co-produced, sang, and played everything on the album, which was engineered by Matt Andrews.

Welch and Rawlings both participated in the recording of 2014's Look Again to the Wind: Johnny Cash's Bitter Tears Revisited, a multi-artist album that paid tribute to Cash's landmark concept album on Native American history. In 2015, Welch sat in on the sessions for the second Dave Rawlings Machine album, Nashville Obsolete. Welch and Rawlings looked back to their first album with the 2016 collection Boots No. 1: The Official Revival Bootleg, which featured unreleased outtakes, alternate versions, and demos from the making of Revival. ~ Jason Ankeny