While attending the University of California, Los Angeles, Locklear began modeling and working in commercials for the school store. She was a member of the Chi Omega sorority at the University of California. In 1979, Locklear landed her first roles appearing in Tales of the Unexpected, and an episode of CHiPs a year later. She landed a few more bit parts in shows, including Eight Is Enough, before Aaron Spelling cast her in the role of Sammy Jo Dean during the second season of his TV series Dynasty. It would be the beginning of a highly successful long-term collaboration with Spelling who, the following year, cast her in the cop show T.J. Hooker with William Shatner. Until the mid 1980s, Locklear would appear as a series regular on T.J. Hooker while making semi-regular appearances on Dynasty. She later became a full-time cast member on Dynasty until its cancellation in 1989.

In the 1990s, after the failed sitcom Going Places and the three-hour mini-series Dynasty: The Reunion, Locklear went on to play another of her best known roles, that of scheming vixen Amanda Woodward on the primetime soap opera Melrose Place. She was originally brought in as a guest star in an attempt to boost the ratings, and her billing in the credits reflected this. Despite eventually becoming a regular cast member in 1993, she continued to be listed as a "Special Guest Star" throughout the entire run of the series until its cancellation in 1999. Locklear also won First Americans in the Arts: Best Actress in a TV series for her role on Melrose Place.

In 2006, her character on the show made Wizard's list of the 100 Greatest Villains of All Time ranked at #49. After the show ended, she was immediately cast on the TV sitcom, Spin City, opposite Michael J. Fox. Locklear starred in the short-lived drama LAX in 2004. Throughout her career, Locklear has starred or guest-starred in no less than seven different television series produced by Aaron Spelling, these being Dynasty, T.J. Hooker, Matt Houston, Fantasy Island, The Love Boat, Hotel, and Melrose Place.

• Flying By (2009) (completed) .... Pamela
  
• Oranges (2009) (V) .... Irene
• Flirting with Forty (2008) (TV) .... Jackie Laurens
• "See Jayne Run" (1 episode)
       - Pilot (????) TV episode
• "Hannah Montana" .... Heather Truscott (1 episode, 2007)
       - Lilly's Mom Has Got It Goin' On (2007) TV episode .... Heather Truscott
• "Rules of Engagement" .... Barbara (2 episodes, 2007)
       - Engagement Party (2007) TV episode .... Barbara
       - Audrey's Sister (2007) TV episode .... Barbara
• Angels Fall (2007) (TV) .... Reese Gilmore
  ... aka Nora Roberts' Angels Fall (Australia) (USA: complete title)
• Women of a Certain Age (2006) (TV) .... Barb
• "Boston Legal" .... Kelly Nolan (2 episodes, 2005)
       - Schadenfreude (2005) TV episode .... Kelly Nolan
       - The Black Widow (2005) TV episode .... Kelly Nolan
• The Perfect Man (2005) .... Jean Hamilton
• "LAX" .... Harley Random (11 episodes, 2004-2005)
       - Cease & Assist (2005) TV episode .... Harley Random
       - Secret Santa (2004) TV episode .... Harley Random
       - Thanksgiving (2004) TV episode .... Harley Random
       - The Pictures to Prove It (2004) TV episode .... Harley Random
       - Out of Control (2004) TV episode .... Harley Random
        (6 more)
• "Two and a Half Men" .... Laura Lang (1 episode, 2004)
       - No Sniffing, No Wowing (2004) TV episode .... Laura Lang
• Looney Tunes: Back in Action (2003) .... Dusty Tails
  ... aka Looney Tunes Back in Action: The Movie (USA: DVD box title)
• Uptown Girls (2003) .... Roma Schleine
• Once Around the Park (2003) (TV) .... Alex Wingfield
• "[scrubs]" .... Julie Keaton (2 episodes, 2002)
       - My Fruit Cups (2002) TV episode .... Julie Keaton
       - My First Step (2002) TV episode .... Julie Keaton
• "Spin City" .... Caitlin Moore (71 episodes, 1999-2002)