Born in Dallas, Loeb studied piano as a child but later switched to guitar. At Brown University, she studied music theory and played as a duo with her roommate. After college, she attended Boston's Berklee School of Music for one semester, but then formed a full band in 1990, christened (in tribute to J.D. Salinger) Nine Stories. Lisa Loeb & Nine Stories began to gig around the Midwest, playing at Austin's South by Southwest seminar. Loeb then hooked up with producer Juan Pati?o, and in early 1992 released the cassette-only Purple Acoustic Tape, which she sold at live shows. Several major labels showed interest in her, but Loeb remained unsigned by late 1993, when her friend Ethan Hawke asked her to contribute a song for his next picture. Director Ben Stiller decided that he liked one of Loeb's other songs even better, so "Stay" was inserted on the soundtrack.

Released as a single in May 1994, it reached number one two months later and eventually sold over 750,000 copies worldwide. Loeb & Nine Stories received a Grammy nomination for Best Pop Performance by a Group, and won a Brit Award for Best International Newcomer. Geffen Records, which had shown interest in Loeb before "Stay," signed her later in 1994 and re-teamed her with Juan Pati?o. Her debut album Tails was released just over a year after her signing, and proved successful with commercial radio as well. Firecracker appeared in 1997, scoring a hit with "I Do." Tours with the Wallflowers and Chris Isaak followed later that summer as well as a stint with the Lilith Fair.

Five years later, Loeb returned with a third effort and her debut for A&M, Cake and Pie. She co-produced the album and collaborated with an impressive cast, which included Glen Ballard, boyfriend Dweezil Zappa, Randy Scruggs (Vince Gill, Sawyer Brown, Waylon Jennings), and Peter Collins $Bon Jovi, the Indigo Girls). First single "The Way It Really Is" was a moderate hit among college radio; "We Could Still Belong Together" was also included on the soundtrack to Legally Blonde. In mid-2002, Loeb inked a deal with Artemis. She relaunced Cake and Pie under the title Hello Lisa, which featured Sanrio's signature Hello Kitty artwork on the cover, that November. The Sanrio/Loeb union proved fruitful, as it coincided with the cutesy character's popularity boom in trendy Hollywood. For her next trick, Loeb reunited with old college pal Elizabeth Mitchell for the children's music album Catch the Moon; it featured a pleasant mix of traditionals and originals. In January 2004, Dweezil & Lisa premiered on Food Network. It followed Zappa and Loeb in the daily lives as rockers and food lovers. Loeb also continued work on a new studio album. The spectacled singer is known for her retro-inspired style and look, her folksy music, as well as her soft melodic voice.