The Chip Ganassi driver crossed the finish line 0.1897 seconds ahead of teammate Scott Dixon.
Despite Wheldon's victory, Sam Hornish Jr., who finished third, clinched his third and Roger Penske's first IndyCar Series title.
"I wasn't going to let this one slip away, I was pretty aggressive," said Wheldon. "I want to thank everybody at Target Chip Ganassi."
Helio Castroneves finished third in the championship with 473 points, two points behind Wheldon and his teammate, Hornish.
Scott Dixon was fourth with 460 points and Victor Meira finished fifth with 411 points.