For Disney, he is known for voicing Lightning McQueen in the Disney/Pixar Cars film series and in the video games Cars, Kinect Rush: A Disney/Pixar Adventure, Cars: Fast as Lightning, and LEGO The Incredibles. In Around the World in 80 Days, Owen, along with his brother, Luke, played the Wright brothers. He also played Roy O'Bannon in the 2000 Touchstone Pictures film, Shanghai Noon and its 2003 sequel Shanghai Knights, Oscar Choice in Armageddon, and Motre Rapid in Breakfast of Champions. He was even mentioned in an episode of Parker Plays.
He is also the middle brother of actors Andrew Wilson and Luke Wilson.
- In an early version of The Emperor's New Groove, then known as Kingdom of the Sun, Owen Wilson was to have voiced that version's counterpart to Pacha, then a young man nearly identical to Kuzco.
- He was considered for the role of Obi-Wan Kenobi in Star Wars: The Phantom Menace.
- He and his brothers all have the same middle name Cunningham (their mother's maiden name).
- To date, he is the first member of the "Frat Pack" to voice a character in any Pixar film.