Six of the top ten seeds have now been eliminated in the opening week of the US Open men's singles, with American ninth seed Taylor Fritz and Italian fifth seed Flavio Cobolli the latest high-profile casualties. Fritz squandered a two-set lead against Argentina's Francisco Cerundolo, while Cobolli collapsed after winning the first set, losing the third to love against Belgium's Alexander Blockx. The upsets have blown the draw wide open, particularly denting hopes of a first American men's champion since Andy Roddick in 2003, though Ben Shelton, Frances Tiafoe, Tommy Paul, Alex Michelsen and Learner Tien remain in contention.

Fritz lost 3-6 4-6 6-3 6-4 6-4 and admitted he could not explain how he let the match slip, saying he needed time away from people. Cobolli fell 6-7 6-3 6-0 6-3, citing low energy and tiredness. Top seed Alexander Zverev progressed with a straight-sets win over Alejandro Tabilo, meaning he and 14th seed Learner Tien are the only top-20 players left in the top half of the draw, potentially allowing Zverev to reach the final without facing a top-10 opponent. Earlier shocks saw fourth seed Novak Djokovic beaten by world number 49 Mariano Navone, 10th seed Arthur Fils lose to Stefanos Tsitsipas, and both third seed Felix Auger-Aliassime and sixth seed Alex de Minaur exit in the second round.