The twin Bryan brothers, Bob and Mike, will not become the first men's doubles team in 62 years to corral a calendar year Grand Slam.
A fourth-seeded duo of 40-year-old Leander Paes and 35-year-old Radek Stepanek ousted the world No. 1 stars 3-6, 6-3, 6-4 on a sunny Thursday at the U.S. Open.
The 35-year-old Bryans were trying to become the first men's doubles team to win all four major events in one year since Ken McGregor and Frank Sedgman turned the trick in 1951.
The Bryans won this year's Australian Open, French Open and Wimbledon events and were the reigning U.S. Open champs prior to Thursday. They beat Paes and Stepanek in last year's finale in Flushing.
The Bryans own four U.S. Open titles among their record 15 major championships. They also captured the gold medal at last year's Olympic Games in London.
The Indian Paes is a seven-time Grand Slam men's doubles champion, including U.S. Open titles in 2006 and 2009, while the Czech veteran Stepanek owns one major doubles title, last year's Aussie Open, which he captured with Paes by upsetting the Bryans in the final in Melbourne.
Paes and Stepanek will meet the second-seeded pairing of Austrian Alexander Peya and Brazilian Bruno Soares in Sunday's final. Peya and Soares handled a 10th-seeded team of Croat Ivan Dodig and Brazil's Marcelo Melo 7-5, 6-4 in the other semi.
Peya and Soares will both play in their first-ever Grand Slam men's doubles final.
Sunday's winning team will split $460,000.