Luke Wilson was born in Dallas, Texas to Irish American parents. The son of an advertising executive and a photographer, he was the youngest of three brothers along with fellow actors Owen and Andrew (the eldest). He attended St. Mark's School of Texas, where he continues to hold the school records for the 400 meter and 800 meter runs.

At Occidental College, Luke was at first more interested in the school's athletics department than he was in drama or theater. He excelled at track and field, but eventually gave up sports after taking a drama class.

Wilson's film acting career began with the lead role in the short film Bottle Rocket in 1994, which was co-written by Wilson's older brother Owen and director Wes Anderson. Bottle Rocket was later made into a feature-length film in 1996.

After moving to Hollywood with his two brothers, he was cast opposite Calista Flockhart with romantic designs in "Telling Lies in America" and made a cameo appearance in the film-within-the-film of "Scream 2" (both 1997). Wilson filmed back-to-back romantic films opposite Drew Barrymore, "Best Men", about a group of friends who pull off a heist on their way to a wedding, and "Home Fries" (both 1998), about two brothers interested in the same woman for very different reasons. (Off-screen, the actor won the girl; he and Barrymore became a couple, but parted ways in 1998.) Wilson remained in demand, playing the doctor beau of a schoolteacher in "Rushmore" (also 1998), directed by Anderson and co-written by brother Owen.

Wilson made his TV debut with a memorable turn as a sheriff in a town populated by vampires in a 1998 episode of Fox's "The X-Files".

Wilson is known for roles in comedies such as Old School and Legally Blonde. He's considered to be a member of the Frat Pack.

He has been romantically linked to actress Drew Barrymore, as well as Gwyneth Paltrow in 2001, before she became involved with Chris Martin from the band Coldplay.