Wilson was born in Dallas, the youngest of three sons of Robert Andrew Wilson, an advertising and television executive, andLaura Cunningham, a photographer.[2] His family, originally fromMassachusetts, is of Irish Catholic descent.[3]
All three Wilson boys attendedSt. Mark's School of Texas. According toOwen, Luke was voted class president the first year he attended St. Mark's.[4] He became interested in acting while attendingOccidental College in Los Angeles.[5]
Wilson's acting career began with the lead role in the short filmBottle Rocket in 1994 which was co-written by his older brother Owen and directorWes Anderson. It was remade as a feature-length film in 1996.[2] After moving to Hollywood with his two brothers, he was cast oppositeCalista Flockhart inTelling Lies in America[2] and made acameo appearance in the film-within-the-film ofScream 2,[2] both in 1997. Wilson filmed back-to-back romantic films in 1998, oppositeDrew Barrymore,Best Men, about a group of friends who pull off a heist on their way to a wedding,[2] andHome Fries which is about two brothers interested in the same woman for different reasons.[2] He played the surgeon beau of a schoolteacher inRushmore (also released in 1998) also directed by Anderson and co-written by his brother Owen.[2]
In 2006, Wilson starred inMy Super Ex-Girlfriend, oppositeUma Thurman, andIdiocracy, a dystopian comedy directed byMike Judge. Wilson portrayed an ordinary serviceman frozen in a cryogenics project. He awakens after hundreds of years in an America which is significantly less intelligent.[8]
In 2023, he starred in theHBO Max animated seriesFired on Mars as Jeffrey Cooper, a graphic designer for a business on Mars whose life is changed upon his termination.
Wilson has written aWright Brothers biopic with his brother Owen, in which they also plan to star.[13]
Wilson was formerly in a relationship withHome Fries co-starDrew Barrymore.[14]
In a 2019 interview, he commented on the fact that he has publicly expressed interest in starting a family since 1996, saying, "I'm 47, I'm ready for that. I need to get to work."[15]