Rookie J.R. Hildebrand appeared well on his way to victory heading into the final turn at IZOD IndyCar Series' premiere event when he got too high along the wall, made contact with it and lost a tire.
The crash allowed Wheldon, making his first start of the year for Bryan Herta Autosport, to cruise into the winner's circle and claim the second Indy 500 championship of his career.
Hildebrand's damaged car limped home for second place, while Graham Rahal came in third followed by Tony Kanaan and Oriol Servia.
Scott Dixon dominated much of the race but ended up in sixth. Defending champ Dario Franchitti also led for much of the event but fell back to 12th place.
Danica Patrick finished 10th in what could have been her final Indy 500 before turning to NASCAR racing.