Tommy Robredo hits heights for Spain
Maria Jose Martinez Sanchez put the two-times champions ahead with a 6-4, 6-4 win over teenager Melanie Oudin, and Robredo beat the 6ft 9in Isner 6-7, 6-3, 7-6.
The Spaniards then teamed up to win the mixed doubles 6-4, 7-5 to complete an impressive 3-0 whitewash.
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Hide AdIsner smashed down 16 aces but Robredo's greater all-round ability eventually proved the difference between the two.
"It's a bit like the casino, red or black," Robredo said, when asked to describe what it is like to face the Isner serve. "If it's red it's the forehand, if it's black it's the backhand, so I am very proud the way I returned."