[5] Kathy Higdon Wilson retired from politics in the late 1980s; switching to a career in early childhood education, she began serving as the director of childcare and development centers in Alexandria, Virginia, in 1991.

[11] Wilson's passion for performing began at an early age, and she has said that her first memorable exposure to theater came when her father took her to New York City to see a production of Cats, inspiring her to create her own plays.

[14] After graduating from NYU in 2002, Wilson and her best friend from college, June Diane Raphael, began studying improvisational comedy at the Upright Citizens Brigade Theater in New York City, where they eventually ran their two-woman sketch show for a number of years.

Comedy Arts Festival in 2005, they were hired by New Regency Pictures to write the film Bride Wars and landed a development deal with UPN to create a sitcom pilot.

[15] Wilson has cited her biggest influences as Catherine O'Hara, Diane Keaton, Madeline Kahn, Lucille Ball, Bette Davis, Molly Shannon, Cheri Oteri, Debra Winger, and Shirley MacLaine.

[3][12][16] Wilson started her comedy career writing and performing with the Upright Citizens Brigade Theatre (UCB) in New York and later in Los Angeles.

She has since appeared in Julie & Julia, C.O.G., The Breakup Girl, The Guilt Trip, Killers, The Brothers Solomon, Freak Dance, The Great Buck Howard, and the Bob Odenkirk-directed short film Derek & Simon: A Bee and a Cigarette.

They wrote and starred together in the comedy Ass Backwards, which co-stars Alicia Silverstone, Jon Cryer, Vincent D'Onofrio, Paul Scheer, and Bob Odenkirk.

Wilson and June Diane Raphael created their newest comedic stage show The Realest Real Housewives, which they star in alongside Jessica St. Clair, Melissa Rauch, Danielle Schneider and Morgan Walsh.

[24] From April 2011 to May 2013, Wilson starred as Penny Hartz in the ABC ensemble comedy series Happy Endings alongside Eliza Coupe, Elisha Cuthbert, Zachary Knighton, Adam Pally and Damon Wayans, Jr. A breakout role for Wilson, she was nominated twice for "Best Supporting Actress in a Comedy Series" at the Critics' Choice Television Awards for her work on seasons two and three of Happy Endings.

In July 2020, the cast reunited over Zoom for the pandemic-themed episode And the Pandemmy goes to... to raise money for the charities Color of Change and World Central Kitchen.

[27] Wilson's other television credits include guest appearances on Black-ish, How I Met Your Mother, The Mindy Project, Drunk History, Grey's Anatomy, Fresh Off the Boat, Kroll Show, Bored to Death, Comedy Bang!

Bang!, The Middle, and The League; she has also had voiceover roles in the animated comedy programs American Dad!, Animals., Archibald's Next Big Thing, Family Guy, Glenn Martin, DDS, and The Life & Times of Tim, as well as in Littlest Pet Shop, where she starred in the series finale episode as Felina Meow.

[citation needed] In 2021, Wilson starred alongside Will Ferrell, Paul Rudd, and Kathryn Hahn in the Apple TV+ mini-series The Shrink Next Door, based on the popular Wondery podcast of the same name.

In addition, her book of essays, The Wreckage of My Presence was published by HarperCollins and made the New York Times bestseller list for non-fiction works.

[28] In 2024, Wilson and Jessica St. Clair wrote and narrated the audiobook The Art of Small Talk, which includes interviews with Amy Poehler, Colin Quinn, Malcolm Gladwell, Tony Hale, and June Diane Raphael, and others.

"[30] Wilson has performed as a number of notable characters on Saturday Night Live: On December 2, 2015, Wilson and comedian Danielle Schneider began hosting the Earwolf podcast Bitch Sesh, where they and a guest have comedic discussions about the previous night's episode of The Real Housewives, as well as other topics related to the Bravo channel and reality television.

Guests have included June Diane Raphael, Andy Cohen, Adam Pally, Jerry O'Connell, Matt Besser, Vanessa Bayer, Michael Rapaport, Elisha Cuthbert, Kristen Wiig, Michelle Collins, and Retta.