Swanson began her acting career at The Actors Workshop with R.J. Adams and promptly moved into TV advertising roles and several one-off appearances in TV series such as Cagney and Lacey and Alfred Hitchcock Presents. In 1986, she debuted on the big screen in two John Hughes films: Pretty In Pink, in a non-speaking role, and Ferris Bueller's Day Off as a character who announces a convoluted excuse for Ferris' absence in class. Her first starring role was later in 1986, in Wes Craven's Deadly Friend as Samantha – "the girl next door". The next year she played Cathy in the adaptation of V. C. Andrews' best-seller Flowers in the Attic.
By 1990, Swanson had made many television appearances, including multiple appearances in Knots Landing (1987–1988), Nightingales (1989), her first starring role in a TV series and a Burt Reynolds television series called B.L. Stryker (1989).
Throughout the 1990s, she starred mostly in films. She played the title role in the 1992 movie Buffy the Vampire Slayer. She appeared in both starring and supporting roles in movies such as Hot Shots!, The Program, The Chase, or her most critically acclaimed role, playing Kristen Connor, a student discovering her sexuality, in John Singleton's Higher Learning. She also appeared in the film adaptation of the comic-book The Phantom and the dark comedy 8 Heads in a Duffel Bag with Joe Pesci
In the 1998–99 season of Early Edition, Swanson played Erica Paget, a love interest of the main character, Gary Hobson. In 1999, Swanson played Vanessa, the girlfriend of Adam Sandler in the movie Big Daddy..
She appeared in and won the 2006 Fox television program Skating with Celebrities, partnered with Lloyd Eisler.
On May 8, 2007, Swanson appeared in the Law & Order: Criminal Intent episode "Bombshell", playing a fictionalized variation on Anna Nicole Smith.
In July 2009, she filmed What If..., co-starring Kevin Sorbo and Debby Ryan, released on August 20, 2010. It was her first theatrical film in 10 years.
Swanson made a cameo appearance in the "Don't You Forget About Me" episode of One Tree Hill, which aired on February 1, 2010. The episode was a homage to John Hughes; Swanson appeared in two films produced by him in the 1980s.
Buffy the Vampire Slayer [1992 Film]