The 34-year-old Brazilian pulled away over the final laps to beat Dan Wheldon and Danica Patrick, who eclipsed her historic fourth-place finish as a rookie in 2005 by crossing the strip of bricks in third.
This day belonged to Castroneves, who pumped his fist all the way down the final straightaway.
"I want to climb the fence," said the driver known as "Spiderman," referring to his signature celebration.
Then he did just that, hopping out of his car after the victory lap and scaling the fence along the main grandstand with his pit crew.
"This is incredible," said Castroneves, who was sobbing as he got the trademark bottle of milk.
Roger Penske earned his record 15th Indy win as a car owner. When he leaned in to hug Castroneves in Victory Lane, the tearful driver said, "Thanks for giving my life back."
Castroneves also claimed the pole and won the pit-stop competition before completing his Indy sweep on race day. Actually, he picked up another victory, as well, learning Friday just before he went out for the final practice that the government had dropped the only remaining tax charge against him. The jury couldn't reach a verdict on one count.
"This is the best month of May ever," Castroneves said.
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