Loeb attended The Hockaday School in Dallas, Texas, one of the top rated private boarding schools in the United States. After graduating in 1986, she went to Brown University where she graduated in 1990 with a degree in comparative literature. She is the first and only unsigned artist to have a number one hit on the American charts, with the song Stay (I Missed You), featured on the soundtrack to the movie Reality Bites and later released on her debut album Tails. Her band Nine Stories is named after the J. D. Salinger collection.
Loeb was discovered by actor and friend Ethan Hawke, who lived in an apartment next to her in New York City. Before contributing Stay to Reality Bites, Loeb had developed a following from her acoustic performances in a New York City coffeehouse. Originally a duet act with another woman Elizabeth Mitchell, the albums Liz and Lisa and Liz and Lisa - Days Were Different were released independently, as was a solo project called The Purple Tape.
Though Stay was her break-through song, Loeb has successful radio hits with other songs from Tails including Do You Sleep?, Taffy and Waiting For Wednesday. The song Hurricane was contributed to the soundtrack for the film Twister. Tails was released in 1994 and achieved platinum status.
In 1997 a sophomore album called Firecracker was released. Though critically praised it did not have the commercial success of Tails, though the single I Do was popular on radio and music television. At this point Lisa also dropped her support band Nine Stories. The single Let's Forget About It was also released.
Loeb did not return to studio recording until 2002's Cake and Pie. The album was a commercial failure and did not receive any major backing or promotion from her record label. She was eventually dropped, and she bought the rights to the masters of the songs from that album. It was re-released independently in late 2002 with the songs rearranged and some deletions/additions. New packaging was also featured, and it was retitled Hello Lisa. In 2003 a children's album, called Catch the Moon, was independently released.
Loeb also dabbles in the acting field. Her debut was in a guest appearance on the television show The Nanny in 1997. She played the voice of a newborn baby in The Rugrats Movie in 1998, and in 1999 was featured as a news reporter in the horror film House on Haunted Hill. 2004 will see the release of the film Serial Killing 4 Dummies which featured Loeb in her largest acting role yet. On January 16, 2004, her television show Dweezil & Lisa first aired on Food Network, in which she shared title billing with her longtime boyfriend Dweezil Zappa.
In early Summer 2004, Loeb announced that her relationship with Dweezil Zappa was over.
Lisa Loeb also was featured as the voice of Mary-Jane Watson in the MTV produced animated show Spider-Man.
In 2004, Loeb changed record labels once again, due to a lack of promotion from her former label Artemis Records, and was signed to the small independent label Zoe/Rounder and her latest album entitled The Way It Really Is, was released August 2004. The album is Loeb's fifth studio recorded album.