She came to notice when she was cast as Jenny Wilder in Little House on the Prairie. She was then cast as the oldest Witherspoon sibling, Kris, on the family drama Our House, which ran from 1986 to 1988. Shannen then went on to appear in an episode of Magnum P.I.

Doherty's first major motion picture role was in Heathers, released in 1989. She went on to star in the Aaron Spelling-produced TV series Beverly Hills 90210 for four years, from 1990 to 1994. Although her departure from the series was reportedly acrimonious, it didn't stop Spelling from casting her in another series, Charmed. She left that series in 2001, after three years (rumors persisted that her departure was against her will, due to a feud with co-star Alyssa Milano). She hosted Scare Tactics on the Sci Fi channel until the 2004 season. She was a former regular on the failed TV series North Shore, a return to her prime-time soap roots.

In 2005, she was cast in the new TV comedy Love Inc. but was dropped from the show just months before the debut in fall.

Doherty will star in her own show, Breaking Up With Shannen Doherty on the Oxygen network this summer.

In late July of 2006 rumors began stating that Doherty had had plastic surgery. In August, tabloid Star Magazine published the first pictures - a cover of the issue can be seen at Doherty Do Over (this issue will see a general release date of August 3rd, 2006). Gossip columnists reported that Doherty was so upset over the front page coverage that she cancelled a shoot for her aforementioned reality TV series. She made an appearance on The View July 31st to counter that she had not had plastic surgery.