Also exiting on an afternoon of high humidity, which eventually descended into an early evening of lightning and torrential rain, was Spanish fourth seed David Ferrer, the highest-ranked casualty in the men's event.
Five-time Grand Slam champion Sharapova -- the 2006 title winner in New York -- was defeated by Danish 10th seed Wozniacki with the 2009 runner-up claiming a deserved 6-4, 2-6, 6-2 triumph on a steamy Arthur Ashe Stadium court to reach the quarter-finals yesterday.
The hot and humid conditions were so punishing that the players were granted a heat break in the locker room before the third set, and when they returned to the court Wozniacki wasted little time, breaking Sharapova to love in the fourth game for a 3-1 lead.
She broke the Russian superstar again in the final game to seal the victory and a chance to play 13th-seeded Italian Sara Errani for a semi-final berth.
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"It means so much to me," said Wozniacki, who reached the semi-finals in 2010 and 2011 but hadn't been past the third round at Flushing Meadows the last two years.
"It's been a bit up and down for me this season," she added. "To win today against a champion like Maria is an unbelievable feeling."
The departure of fifth-seeded Sharapova leaves just two of the women's top eight left -- world number one and two-time defending champion Serena Williams and seventh-seeded Canadian Eugenie Bouchard.
"I thought she played really well. She made me hit a lot of balls. That's always been her strength. But she did extremely well today. She's a great retriever, especially in these types of conditions. I just felt like I maybe went for a little too much," said Sharapova.