Deschanel appeared in a guest role on the television series Veronica's Closet before making her film debut in Lawrence Kasdan’s 1999 comedy Mumford, and later in the year she appeared in the music video for The Offspring's single "She's Got Issues". In her second film, director Cameron Crowe's autobiographical Almost Famous (2000), Deschanel played Anita Miller, the protagonist's rebellious older sister. The film received critical praise, but was not a box office success. Deschanel continued to sing, and in 2001 formed If All the Stars Were Pretty Babies, a jazz cabaret act with fellow actress Samantha Shelton. The pair performs around Los Angeles on an ad-hoc basis.

Deschanel played supporting roles in a series of films that included Manic (2001), Big Trouble (2002), Abandon (2002), and The Good Girl (2002). In late 2002, The New York Times reported that Deschanel was "one of Hollywood's most sought-after young stars," and the Los Angeles Times wrote in early 2003 that Desc