The sixth seed overpowered the Spaniard in two hours, 20 minutes of outstanding hitting to set up a final against either five-times champion Roger Federer or fourth seed Novak Djokovic of Serbia.
"It's very difficult for me to speak at this moment. This is my favourite tournament and I can't believe this moment," a beaming Del Potro said in a courtside interview.
"I am very close to my dream, to win this tournament. I hope I can do it. I am very happy to be here. Tomorrow I will fight until the final point, if I win or lose, I think this is the best moment of my life."
Nadal went into the match struggling with a right abdominal injury and his service speed was clearly down, allowing Del Potro to be aggressive on his returns.
The first set was a story of missed opportunities as Nadal squandered three break point chances, while the Argentine broke twice, in the fourth and eighth games.
The pattern was repeated in the second set and though Nadal continued to fight in the third, Del Potro was too strong and cruised to a comprehensive victory.
The scoreline represented the heaviest grand slam defeat of Nadal's career.
"It was a little bit unlucky year for me," Nadal said. "I started the year playing really well but that's sport.
"In Cincinnati (last month) and here, I had a problem with the right abdominal and it was difficult for me to serve.
"But he is playing very well and I am very happy for him."
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