Wise Dan raced farther back than usual through the early stages of the race and advanced quickly around the turn.
Za Approval took the lead early in the stretch run and ran on strongly but Wise Dan ranged up on his outside to win by a length, notching his second straight win in the Mile. Silentio was a long shot third and Za Approval faded to finish fourth.
European hopes Olympic Glory and Cristoforo Colombo were never factors as the mile race on firm turf went in 1:32.47.
Wise Dan took U.S. Horse of the Year honors last year with a victory over Animal Kingdom in the Mile. That race came amid a nine-race victory skein that was broken last month as he succumbed to Silver Max in the Grade I Shadwell Turf Mile at Keeneland. Silver Max finished fourth in Saturday's race.
Owner Morton Fink said he is not considering retiring the 6-year-old Wiseman's Ferry gelding. "As long as he goes, I'll go with him," Fink said.