His television career started in 2003 with a token role in the TV series Hope & Faith followed by brief appearances in The New Twenty and Ugly Betty. After many small roles on television, in 2012, he had a lead role in the feature film Gayby which debuted at the SXSW festival. In the film, Matt a comic book store worker (played by Wilkas) and Jenn a yoga instructor (played by Jenn Harris), best friends from college, now single and in their thirties, in agreement with a pact they had made in their youth, decide to have a baby ("gayby") together, even though Jenn is straight and Matt is gay. In 2012, Wilkas and Harris co-won the Ashland Independent Film Award for "Best Acting Ensemble: Feature" during the Ashland Independent Film Festival for their roles in Gayby. The film won a number of other festival awards, named one of the top ten independent films of 2012 by IndieWire, and nominated for an Independent Spirit Award. For his performance in the film, Wilkas was named one of Out magazine's "Out100" and one of The Los Angeles Outfest Film Festival's "Five in Focus".
Wilkas co-wrote with American actor and Playwright Mark Setlock titled Pageant Play, a satire about the world of child beauty pageants. The play was produced in July 2008 at the Berkshire Theatre Festival. and in 2012, he was in the stage production Spider-Man: Turn Off the Dark replacing main actor Matt Caplan. Wilkas has appeared on stage in a number of acts including Silence! (The Musical), The Last Sunday in June, Far and Wide, The Pride etc. He has appeared in The Williamstown Theatre Festival, The Huntington Theatre Company, The Berkshire Theatre Festival, The Rattlestick Playwrights Theater, and The Sundance Theatre Institute, under the direction of Michael Greif, Anna D. Shapiro, Will Frears, Carolyn Cantor, Mark Brokaw, Nicholas Martin, and Trip Cullman.
In 2014, Wilkas appeared in Undateable, an American television sitcom that aired on NBC where he was cast as the character Brett, Justin Kearney's gay friend. He also appeared in a number of shorts including This Bachelorette Party Sucks and Masc Only.
Matthew Wilkas is openly gay. Since November 2015, he has been in a relationship with freestyle skiing champion and Olympic athlete Gus Kenworthy. At the 2018 Winter Olympics, in Pyeongchang, South Korea, Wilkas kissed Kenworthy before his qualifying run in the men's slopestyle; the kiss was broadcast on live television and was lauded as being a significant moment in visibility of LGBT+ athletes.
In 2017, he had a lead role in New York Is Dead, a series that he co-wrote and produced. As Felix, he co-stars with Gayby Actress Jenn Harris. Also in 2017, he is appearing in a lead role as X in "Boy Culture: The Series", an episodic sequel to the original 2006 LGBT American drama film Boy Culture. A Kickstarter campaign was launched for the production. The series will also include Darryl Stephens (as Andrew), Matthew Crawford (as Chayce), as well as Stephen Guarino and singer Steve Grand.
