Wheldon, a native of England, won the Indy 500 twice, earlier this year and in 2005. He hadn't won a race in two years when he took over the lead in the last lap of this year's Indy 500, winning for Bryan Herta Autosport after an accident took out leader JR Hildebrand.
"This was more of an emotional win than in 2005," Wheldon told reporters after the May race. "I'm in a different stage of my life."
At today's Las Vegas Motor Speedway race, Wheldon's car went airborne and flew over other cars during Lap 13. He was removed from the car and airlifted to the hospital but died from his injuries.
The wreck, coming out of Lap 2 on the Vegas track, has been described as one of the worst seen on the IndyCar circuit.
Wheldon had told USA Today earlier this weekend that "things haven't been going well" with the car but had expressed hope that his 34th-place start in a 34-car field at the IZOD IndyCar World Championships still would end up with a victory.
Teammates were notified at a post-meeting race. Three other drivers were also injured in the race, according to the Los Angeles Times.
Other drivers--including Danica Patrick in her final IndyCar start--had expressed concerns over the 225-mph speeds posted at the track during practice laps.