Leander Paes and Radek Stepanek stunned top-seeded and hot favourite pair of Mike and Bob Bryan 3-6 6-3 6-4 in the semi-finals.
American twins were trying to become first doubles team since 1951 to collect all four Grand Slam titles in the same year.
Defending champion Andy Murray was ousted from the US Open, falling to Swiss ninth seed Stanislas Wawrinka 6-4, 6-3, 6-2 in a quarter-final shocker at Arthur Ashe Stadium.
Wawrinka reached his first Grand Slam semi-final by stunning the reigning Olympic and Wimbledon champion, booking a Saturday last-four date against world number one Novak Djokovic.
"It feels amazing for sure, especially after that match against the defending champion. It was a crazy match for me to beat him in three sets," Wawrinka said after the match.
Top seed Novak Djokovic defeated 21st-seeded Mikhail Youzhny of Russia 6-3, 6-2, 3-6, 6-0, to set up a semis clash with Stanislas Wawrinka.
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