For Disney, he is known for voicing Lightning McQueen in the Cars film series and in the video games Cars, Kinect Rush: A Disney/Pixar Adventure and Cars: Fast as Lightning. 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.
- 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).