The No. 26 Andretti Green Racing Honda crossed the finish line ahead of runner-up Vitor Meira while the cars were running under caution.
"This has been a dream come true for me," said Wheldon. "The best drivers in the world and the best teams in the world are here and I'm just so proud. Thank you everybody."
For Wheldon, the current Indy Racing League points leader, it was his first Indy victory and fourth IRL win in five races this season.
Dan Wheldon of Great Britain soaks himself with the traditional bottle of milk after winning the Indianapolis 500 on Sunday. (AP Photo/Michael Conroy)
"I'm in shock, Dan ran a helluva race," said Mario Andretti, who went 0-for-14 at the Indy as a driver. "I feel as good as if I won it myself."
Patrick narrowly missed becoming the first woman to leave Indianapolis Motor Speedway as the winner.
The 23-year-old finished fourth, the best showing of the four females who have qualified for the Indianapolis 500.
Bryan Herta and Buddy Lazier rounded out the top-five finishers.
It was a bad day for Canada's two drivers in Indianapolis.
Patrick Carpentier finished 21st overall, after being knocked out of the race when his car ran into debris on the track at lap 153. Compatriot Marty Roth finished 31st, after twice receiving the black flag for running too slowly.
Patrick, who drives for the Rahal-Letterman team, was the first woman ever with a realistic chance of prevailing.
Ahead of everyone on lap 56, she became the first woman to lead a lap at the popular event.
Patrick continued to stalk the leaders until lap 80 when she made a rookie mistake.
She was running in fourth when she stalled her car coming out of the pits. It dropped her all the way to 16th place. But it didn't stop Patrick. She returned to the top-10 on lap 140.
When the leaders came for fuel for the final time on lap 171, Patrick stayed on the track and inherited the lead.
The race restarted on lap 175. Wheldon, third on the track but in second place struggled to get past a backmarker which allowed Patrick to get a comfortable lead.
Wheldon had plenty in the tank while Patrick was forced to conserve fuel. It showed as Wheldon charged towards Patrick and passed her on lap 186 just as Kosuke Matsuura was spinning out.
The race would restart with 10 laps to go and Patrick amazingly grabbed the lead again with a move underneath Wheldon. But Patrick could no longer keep up the pace or finish the race without stopping.
Wheldon charged past Patrick with seven laps to go. Her teammate Meira passed her as did Herta.
A final caution for a Sebastian Bourdais crash brought out the yellow and white flag and the race ended under caution with Wheldon taking the checkered flag at a pedestrian 65 miles per hour.
with files from Sports Network
