He is known for his roles in films such as Bottle Rocket (1996), Blue Streak (1999), My Dog Skip (2000), Legally Blonde (2001), The Royal Tenenbaums (2001), Old School (2003), My Super Ex-Girlfriend (2006), Idiocracy (2006), You Kill Me (2007), The Skeleton Twins (2014), Meadowland (2015) and Brad's Status (2017).

On television, he played Casey Kelso on That '70s Show (2002–2005), Levi Callow on Enlightened (2011–2013) and Pat Dugan / S.T.R.I.P.E.

Wilson's acting career began with the lead role in the short film Bottle Rocket in 1994 which was co-written by his older brother Owen and director Wes Anderson.

[2] After moving to Hollywood with his two brothers, he was cast opposite Calista Flockhart in Telling Lies in America[2] and made a cameo appearance in the film-within-the-film of Scream 2,[2] both in 1997.

[2] He played the physician beau of a schoolteacher in Rushmore (also released in 1998) also directed by Anderson and co-written by his brother Owen.

[7] In 2006, Wilson starred in My Super Ex-Girlfriend, opposite Uma Thurman, and Idiocracy, a dystopian comedy directed by Mike Judge.

In the same year, he appeared in You Kill Me, 3:10 to Yuma, Blades of Glory, and worked on Henry Poole is Here in La Mirada, California which was released in 2008.