| Movie | 2006 | Brother Bear 2 | Innoko (voice) | |
| Movie | 2001 | Pootie Tang | Biggie Shorty | |
| Movie | 2007 | Evan Almighty | Rita | |
| Movie | 2005 | Monster-in-Law | Ruby | |
| Movie | 2006 | My Super Ex-Girlfriend | Carla Dunkirk | |
| Movie | 2006 | Over the Hedge | Stella (voice) | |
| Movie | 2000 | Nutty Professor II: The Klumps | Chantal | |
| Movie | 2009 | Wanda Sykes: I'ma Be Me | Herself | |
| Movie | 2006 | Wanda Sykes: Sick and Tired | Herself | |
| Movie | 2003 | Richard Pryor: I Ain't Dead Yet, #*%$#@!! | Self | |
| Movie | 2006 | Barnyard | Bessy (voice) | |
| Movie | 2001 | Down to Earth | Wanda | |
| Movie | 2011 | Rio | Chloe / Goose (voice) | |
| Movie | 2023 | Wanda Sykes: I'm an Entertainer | Self | |
| Movie | 2003 | Wanda Sykes: Tongue Untied | Herself | |
| Movie | 2012 | Ice Age: Continental Drift | Granny (voice) | |
| Movie | 2020 | Noah's Arc: The 'Rona Chronicles | | |
| Movie | 2013 | The Hot Flashes | Florine Clarkston | |
| Movie | 1998 | Tomorrow Night | Wanda | |
| Movie | 2013 | The Out List | Herself | |
| Movie | 2022 | Stand Out: An LGBTQ+ Celebration | | |
| Movie | 2023 | Albert Brooks: Defending My Life | Self | |
| Movie | 2005 | Just for Laughs Stand Up, Vol. 1: Best of the Uptown Comics | Herself | |
| Movie | 2024 | Saving Bikini Bottom: The Sandy Cheeks Movie | Sue Nahmee | |
| Movie | 2005 | Earth to America | Self | |
| Movie | 2016 | Ice Age: Collision Course | Granny (voice) | |
| Movie | 2025 | Undercard | Cheryl 'No Mercy' Stewart | |
| Movie | 2006 | The Adventures of Brer Rabbit | Sister Moon (voice) | |
| Movie | 2006 | Hammy's Boomerang Adventure | Stella (voice) | |
| Movie | 2024 | Outstanding: A Comedy Revolution | Self | |
| Movie | 2006 | Clerks II | Wife | |
| Movie | 2017 | Snatched | Ruth | |
| Movie | N/A | Tangles | | |
| Movie | 2016 | Wanda Sykes: What Happened… Ms. Sykes? | Herself | |
| Movie | 2016 | Bad Moms | Dr. Elizabeth Karl | |
| Movie | 2006 | Back to the Well: 'Clerks II' | Self / Wife | |
| Movie | 2017 | A Bad Moms Christmas | Dr. Elizabeth Karl | |
| Movie | 2018 | Hurricane Bianca: From Russia with Hate | Prison Matron | |
| Movie | 2020 | Friendsgiving | Fairy Gay Mother #1 | |
| Movie | 2019 | The Wedding Year | Janet / Grandma | |
| Movie | 2015 | How to Vajaculate: If You Build It, She Will Come | Goddess | |
| Movie | 2019 | UglyDolls | Wage (voice) | |
| Movie | 2019 | Wanda Sykes: Not Normal | Herself | |
| Movie | 2003 | MTV Reloaded | The Oracle | |
| Movie | 2021 | Breaking News in Yuba County | Rita | |
| Movie | 2019 | Live in Front of a Studio Audience: Norman Lear's "All in the Family" and "The Jeffersons" | Louise Jefferson | |
| Movie | 2019 | Jexi | Denice | |
| Movie | 2007 | License to Wed | Doctor (uncredited) | |
| Movie | 2016 | Do I Look Like a Lady? (Comedians and Singers) | Self (archive footage) | |
| Movie | 2020 | Feeding America Comedy Festival | Self | |
| Movie | 2001 | Best of the Chris Rock Show: Volume 2 | | |
| Movie | 2006 | World's Greatest Stand Up: Volume One | self | |
| Movie | 2021 | Roll Up Your Sleeves | Self | |
| Movie | 2021 | The One and Only Dick Gregory | Self | |
| Movie | 2024 | Underwater Projects | Narrator | |
| Movie | 2021 | The Upshaws - The Afterparty | Self | |
| Movie | N/A | Deck the Y'alls | | |
| TV Show | 2003 | The Ellen DeGeneres Show | Self | 6 |
| TV Show | 1996 | The Daily Show | Self | 4 |
| TV Show | 2004 | Wanda Does It | | 6 |
| TV Show | 1952 | Today | Self | 1 |
| TV Show | 1997 | The View | Self | 4 |
| TV Show | 1992 | The Tonight Show with Jay Leno | Self | 15 |
| TV Show | 2012 | Inside Comedy | Self | 1 |
| TV Show | 1999 | The Early Show | Self - Guest | 2 |
| TV Show | 2012 | Finding Your Roots | Self | 1 |
| TV Show | 2020 | The Holiday Movies That Made Us | Self (archive footage) | 1 |
| TV Show | 2021 | The Upshaws | Lucretia | 48 |
| TV Show | 2006 | The New Adventures of Old Christine | Barb Baran | 67 |
| TV Show | 1998 | Comedy Central Presents | | 1 |
| TV Show | 1998 | Will & Grace | Cricket | 1 |
| TV Show | 2009 | The Jay Leno Show | Self | 2 |
| TV Show | 1995 | MADtv | Self | 1 |
| TV Show | 1993 | Late Night with Conan O'Brien | Self - Guest | 4 |
| TV Show | 1997 | The Chris Rock Show | | 17 |
| TV Show | 2003 | Wanda at Large | Wanda Mildred Hawkins | 19 |
| TV Show | 1997 | Premium Blend | Host | 97 |
| TV Show | 1997 | The View | Self - Guest | 2 |
| TV Show | 2009 | Drop Dead Diva | Judge Yvonne Wright | 1 |
| TV Show | 2021 | Q-Force | Deb (voice) | 10 |
| TV Show | 2001 | The Downer Channel | | 6 |
| TV Show | 2019 | A Black Lady Sketch Show | Heckler | 1 |
| TV Show | 2015 | The Late Show with Stephen Colbert | Self | 3 |
| TV Show | 2008 | The Wendy Williams Show | | 1 |
| TV Show | 2009 | The Wanda Sykes Show | | 22 |
| TV Show | 2022 | Alabama Jackson | Harriet Tubman | 7 |
| TV Show | 2014 | Last Week Tonight with John Oliver | Self | 1 |
| TV Show | 2019 | The Other Two | Shuli Kucerac | 19 |
| TV Show | 2017 | The Good Fight | Allegra Durado | 3 |
| TV Show | 2013 | Alpha House | Senator Rosalyn DuPeche | 14 |
| TV Show | 2005 | The Late Late Show with Craig Ferguson | Self | 1 |
| TV Show | 2018 | The Shop | Self | 1 |
| TV Show | 2014 | Late Night with Seth Meyers | Self | 5 |
| TV Show | 2003 | Jimmy Kimmel Live! | Self | 7 |
| TV Show | 2000 | Curb Your Enthusiasm | Wanda | 9 |
| TV Show | 2004 | Miley's New Year's Eve Party | Self - Guest | 1 |
| TV Show | 2016 | Chelsea | Self | 2 |
| TV Show | 2016 | Ask the Storybots | | 1 |
| TV Show | 2015 | The Late Late Show with James Corden | Self - Guest | 1 |
| TV Show | 2014 | Penn Zero: Part-Time Hero | Shirley B. Awesome (voice) | 2 |
| TV Show | 2011 | Ridiculousness | Self | 1 |
| TV Show | 2011 | Bob's Burgers | Sofa Queen (voice) | 1 |
| TV Show | 2015 | Hot Ones | Self | 1 |
| TV Show | 1953 | The Oscars | Self - Host | 1 |
| TV Show | 2007 | Back at the Barnyard | Bessy | 97 |
| TV Show | 2015 | Lip Sync Battle | Self | 1 |
| TV Show | 2022 | Sherri | Self - Guest | 4 |
| TV Show | 1988 | LIVE with Kelly and Mark | Self - Guest | 1 |
| TV Show | 2015 | Celebrity Family Feud | Self | 1 |
| TV Show | 2014 | Broad City | Dara | 3 |
| TV Show | 2016 | Martha & Snoop's Potluck Dinner Party | | 1 |
| TV Show | 2018 | Summer Camp Island | Ethel (voice) | 1 |
| TV Show | 2007 | The Graham Norton Show | Self | 1 |
| TV Show | 2019 | Harley Quinn | Queen of Fables (voice) | 3 |
| TV Show | 2014 | black-ish | Daphne Lido | 16 |
| TV Show | 2018 | Vampirina: Ghoul Girls Rock! | | 15 |
| TV Show | 2009 | Watch What Happens Live with Andy Cohen | Self - Guest | 3 |
| TV Show | 2009 | RuPaul's Drag Race | Self - Guest Judge | 1 |
| TV Show | 2016 | To Tell the Truth | Self - Panelist | 1 |
| TV Show | 2023 | Velma | Krista (voice) | 1 |
| TV Show | 2024 | Good Times | Mrs. Likeigiveashit (voice) | 1 |
| TV Show | 2019 | The Kelly Clarkson Show | Self | 1 |
| TV Show | 2015 | Jay Leno's Garage | Self | 1 |
| TV Show | 2021 | Star Wars: The Bad Batch | Phee Genoa (voice) | 7 |
| TV Show | 2022 | The Jennifer Hudson Show | Self | 1 |
| TV Show | 1989 | The Simpsons | Therapist (voice) | 1 |
| TV Show | 1999 | Futurama | Bev (voice) | 1 |
| TV Show | 2020 | Visible: Out on Television | Self | 5 |
| TV Show | 2003 | Real Time with Bill Maher | Self | 1 |
| TV Show | 2023 | Velma | Linda (voice) | 16 |
| TV Show | 1996 | The Daily Show | Self - Guest Host | 4 |
| TV Show | 2017 | Big Mouth | Ghost of Harriet Tubman (voice) | 1 |
| TV Show | 2023 | History of the World: Part II | Various Characters | 8 |
| TV Show | 2019 | Scooby-Doo and Guess Who? | Wanda Sykes (voice) | 1 |
| TV Show | 2023 | Rock, Paper, Scissors | Dian (voice) | 1 |
| TV Show | 1995 | The Drew Carey Show | Christine Watson | 3 |
| TV Show | 1993 | Late Night with Conan O'Brien | Self | 1 |
| TV Show | 2014 | BoJack Horseman | Mary-Beth (voice) | 1 |
| TV Show | 2010 | Conan | Self | 3 |
| TV Show | 2006 | The Megan Mullally Show | Self - Guest | 1 |
| TV Show | 2022 | Chivalry | Jean Shrill | 5 |
| TV Show | 2018 | Lie Detector | Self | 1 |
| TV Show | 2025 | Lil Kev | Nancy (voice) | 10 |
| TV Show | 2022 | Gutsy | Self | 1 |
| TV Show | 2019 | The Kelly Clarkson Show | Self - Guest Host | 1 |
| TV Show | 1995 | Dr. Katz, Professional Therapist | Wanda (voice) | 2 |
| TV Show | 2025 | Everybody's Live with John Mulaney | Self - Comedian | 1 |
| TV Show | 2013 | Hollywood Game Night | Self | 1 |
