Her first break after college was a spot in Billy Crystal’s 1984 music video You Look Marvelous. Her first television appearances began in 1985 with brief stints on St. Elsewhere, MacGyver, and Cheers. She also made guest appearances on Matlock, Murphy Brown, Herman's Head, Star Trek: The Next Generation, Blossom, as well as a recurring role on the cult favorite Twin Peaks. By the mid-90s, she was a regular guest player on dozens of series, with prominent recurring roles on 3rd Rock From the Sun and Party of Five. Strong also appeared on ER, Picket Fences, Silk Stalkings and Dawson's Creek. One of Strong's most prominent roles during the 1990s was a recurring stint as Elaine’s nemesis Sue Ellen Mischke, the “bra-less wonder” and candy bar heiress, on several episodes of the hit sitcom Seinfeld.

She is well known to viewers for recurring roles on Sports Night, in which she played Sally Sasser, the nemesis of Felicity Huffman's Dana Whitaker. She also guest starred on The WB's popular 7th Heaven, Gilmore Girls and Everwood. While working for The WB, she also managed to squeeze in guest appearances on Ally McBeal, Nip/Tuck, CSI, Malcolm in the Middle, and the short-lived The Lyon’s Den. Strong appeared in movies such as Spaceballs, The Deep End of the Ocean, Red Dragon, Exposed, Starship Troopers and Starship Troopers 2 (curiously she died in the original but returned in a different role in the second movie). More recently, she can be seen in the dramatic Lifetime movie Family in Hiding which premiered on August 6, 2006 as well as Curb Your Enthusiasm where she plays a love interest of Larry David. Although she stars on Desperate Housewives, Strong has recently made an appearance on sister ABC program Boston Legal as a judge hearing Denny Crane's case.

Strong currently appears on the ABC hit dramedy Desperate Housewives, opposite Felicity Huffman, Marcia Cross, Eva Longoria, Nicolette Sheridan, Dana Delany and Teri Hatcher. She plays the deceased Mary Alice Young, who narrates the events of her friends' and neighbors' lives from beyond the grave. She can be heard in every episode of the series (which was sparked by Mary Alice's death) with the exception of one narrated by Rex Van de Kamp (portrayed by Steven Culp from 2004-2005), and she appears several times in flashbacks where Mary Alice is still alive. Long before her now popular role on Desperate Housewives, she played a "desperate housewife" in Undercurrent (1999), starring Lorenzo Lamas. She played another deceased wife on the television series Everwood, appearing mainly in flashback sequences as the late Julia Brown. Marcia Cross, her Desperate Housewives co-star, also appeared on Everwood for a season playing Dr. Linda Abbott, the love interest of the Julia Brown's widower, Dr. Andrew Brown. While Brenda remains mostly off-air and heard only, both she and the producer Marc Cherry feel that her character is most essential to the entity of the series. Strong also admitted that she does not feel ostracized by the on-air talents. Strong attends functions related to the show just as do the others.

• Privileged (2009) (post-production) .... Mrs. Carrington
• You (2008) (post-production) .... Paula
  
• "Desperate Housewives" .... Mary Alice Young (106 episodes, 2004-2008)
       - A Vision's Just a Vision (2008) TV episode (voice) .... Mary Alice Young
       - Me and My Town (2008) TV episode (voice) .... Mary Alice Young
       - City on Fire (2008) TV episode (voice) .... Mary Alice Young
       - What More Do I Need? (2008) TV episode (voice) .... Mary Alice Young
       - There's Always a Woman (2008) TV episode (voice) .... Mary Alice Young
        (101 more)
• "Boston Legal" .... Judge Judy Beacon (1 episode, 2008)
       - True Love (2008) TV episode .... Judge Judy Beacon
• "Law & Order: Criminal Intent" .... Kathy Jarrow (1 episode, 2008)
  ... aka Law & Order: CI (USA: promotional abbreviation)
       - Betrayed (2008) TV episode .... Kathy Jarrow
• The Adventures of Young Indiana Jones: Scandal of 1920 (2008) (V) .... Beatrice Kaufman
• Ocean of Pearls (2008) .... Mary Stewart
• "Shark" .... Olivia Hartnell (1 episode, 2007)
       - In Absentia (2007) TV episode .... Olivia Hartnell
• "Curb Your Enthusiasm" .... Dr. Susan Flomm (1 episode, 2007)
       - The N Word (2007) TV episode .... Dr. Susan Flomm
• A Plumm Summer (2007) .... Viv
• "Help Me Help You" .... Linda (3 episodes, 2006)
       - The Sheriff (2006) TV episode .... Linda
       - Perserverance (2006) TV episode .... Linda
       - Working Women (????) TV episode .... Linda
• The Work and the Glory III: A House Divided (2006) .... Mary Ann Steed
• Scarface: The World Is Yours (2006) (VG) (voice)
• Desperate Housewives: The Game (2006) (VG) (voice) .... Mary Alice Young
• "Just Legal" .... Liza Lynch (1 episode, 2006)
       - The Bar (2006) TV episode .... Liza Lynch
• Family in Hiding (2006) (TV) .... Carol Peterson
• The Kid & I (2005) .... Bonnie Roman