Guthrie was born in Massachusetts as the youngest daughter of world-renowned folksinger Arlo Guthrie and the granddaughter of the legendary Woody Guthrie. As a third generation singer/songwriter Guthrie released her first self-titled album on the family-owned-and-operated Rising Son Records in 2002. As a child she was involved in theater and dance. Her first recorded appearance was as a vocalist on dad's 1981 album Power of Love. Her interest in music was sparked when she worked as her father's road manager on the 1997 Further Festival tour. She picked up an acoustic guitar and started playing as a way to join in on the fun. "I always wrote poems, so it wasn't that far off for me to turn that into songs."
"My dad was absolutely thrilled, of course, and would teach me stuff every day when we were on the road together. That was a really cool way to get to know my dad, because I'd never known him that way. And that's another thing that made it easy: my dad was so supportive.Her live debut was with family and friends at Carnegie Hall. In 1997, she met her future husband, Johnny Irion. Guthrie and Irion were married on October 16, 1999 and began performing together as Sarah Lee Guthrie & Johnny Irion in the fall of 2000.