Loeb's efforts now include music, film, television, voice-over work and children’s recordings. Her five studio CDs include her major label debut, the gold-selling Tails and its follow-up, the Grammy-nominated, gold-selling Firecracker. Loeb has appeared in two television series, Dweezil & Lisa, a weekly culinary adventure for the Food Network and Number 1 Single, a dating show on the E! Network in 2006.

In conjunction with Camp Lisa, she launched her own non-profit, The Camp Lisa Foundation, designed to help underprivileged kids attend summer camp through its partnership with Summer Camp Opportunities Provide an Edge, Inc. (S.C.O.P.E.).

Loeb was born in Bethesda, Maryland, and raised in Dallas, Texas where she attended The Hockaday School, an all-girls private school. Her parents still live in Dallas, where her mother is a homemaker and her father, Dr. Peter Loeb, is a gastroenterologist. She has three siblings, all involved with music: conductor Benjamin Loeb, musician Debbie Loeb, and mixing-engineer Philip Loeb. After graduating from high school in 1986, she went to Brown University, where she graduated in 1990 with a degree in comparative literature. At Brown, she and Elizabeth Mitchell formed a band named Liz and Lisa, including future singer/songwriter and Brown classmate Duncan Sheik as a guitarist. The duo released the albums Liz and Lisa (1989) and Liz and Lisa: Days Were Different (1990) independently. After college, the jazz/rock bassist Rick Lassiter and TV and film composer/drummer Chad Fisher joined the band.

After developing a following together, Loeb and Mitchell parted ways a few years after college. Loeb began working with Juan Patiño to make the Purple Tape, the violet cassette that Loeb used as a sonic calling card to industry gatekeepers and that fans could buy at her gigs. Produced by Patiño and recorded at his apartment on 52nd Street in 1992, the cassette includes the earliest recordings of several Loeb favorites including “Do You Sleep,” “Snow Day,” “Train Songs,” and “It’s Over.” Loeb also took this time to record her band playing some other songs, one of which was "Stay (I Missed You)." During the same time, she was recording a band demo with Kevin Salem for a record company demo deal.

Loeb had also developed a following from her solo acoustic performances on the New York City coffeehouse circuit and the rock club circuit. She travelled to cities such as Philadelphia, Los Angeles, Dallas, but focused mainly on New York City. She played acoustically and with her band in folk and rock clubs, including The Bitter End, CBGB’s, CB's Gallery, The Wetlands, Lonestar Roadhouse and more. Loeb also performed at several music festivals, such as the New Music Seminar and South by Southwest.

Loeb's big break came when she was discovered by actor Ethan Hawke, who lived in an apartment across the street from her in New York City. They met through mutual friends in the NYC theater community. Loeb gave Hawke the Juan Patiño-produced version of "Stay (I Missed You)", who in turn gave it to director Ben Stiller during the making of the 1994 film Reality Bites. Stiller subsequently decided to use the song in the film’s ending credits, and Ron Fair decided to put it on the soundtrack on RCA records. "Stay" ultimately went on to become a number one hit on the American charts. When her song hit number one, Loeb earned the distinction of being the only artist to top the Hot 100 before being signed to any record label. Hawke also directed a rare one-take video of “Stay” with no edits.

In September 1995, Loeb's debut album, Tails, was released. The album was co-produced by Juan Patiño, her then longtime boyfriend. Although none of the singles from Tails matched the breakthrough appeal of "Stay" (which was also included on this album), Loeb still managed a top 20 hit with "Do You Sleep?" and two moderately successful radio hits with "Taffy" and "Waiting for Wednesday". Tails went on to achieve Gold status.

In 1997, Loeb released a second major-label album, Firecracker, and began experimenting even more with orchestrations done with Dan Coleman. At this point, Loeb started going under her own name for the albums instead of using the band name, Nine Stories (named after the J. D. Salinger collection), although she still continued to tour worldwide with the band and acoustically as she had done from the start. Critically praised, Firecracker included hit singles such as "I Do," which received radio success, peaking at #17 on the Billboard Hot 100 and music television.

In 2000, Loeb participated in the Ozzy Osbourne tribute album Bat Head Soup performing "Goodbye to Romance" with Dweezil Zappa on guitar. She also contributed to An All Star Tribute To Cher with “Gypsies, Tramps and Thieves,” and to An All Star Tribute To Shania Twain with “Don’t Be Stupid,” both of which were released in 2005.

Her greatest hits compilation, The Very Best of Lisa Loeb, was released as a cassingle through Universal in January 2006 as well as a Japanese version of the album. Other international work includes Loeb’s guest performance on the song “Anti-Hero” for an all-female Japanese musical group Rin''s album Inland Sea. In 2006, Loeb contributed to the album A World of Happiness, designed to disseminate messages of kindness, compassion, tolerance, and self-reliance to children of all ages, performing as Lady Leonali the Ladybug singing “In the Details.” Loeb contributed vocals to New Found Glory's cover of "Stay," from their 2007 LP From the Screen to Your Stereo Part II, as well as performing the song live with the band. Though Reality Bites was the first, Loeb’s music has been featured in additional soundtracks. The popular single "How" was included on the soundtracks for films Twister and Jack Frost, and was heard in the Buffy the Vampire Slayer episode "Homecoming." “We Could Still Belong Together” earned a spot on the Legally Blonde soundtrack (2001), while “I Wish” can be heard on the soundtrack for Anywhere But Here (1999).