Andy Murray's comeback from hip surgery came to an end in the second round after a 6-2 6-3 6-4 defeat to Felix Auger-Aliassime.
Johanna Konta was also a casualty, losing 2-6 7-6 (5) 6-4 to world number 77 Sorana Cirstea.
Meanwhile, Serena Williams moved a step closer to a record-equalling 24th grand slam title with a straight-sets win over Margarita Gasparyan.
Here, the PA news agency looks back at day four at the US Open.
Picture of the day
Shot of the day
Why go over the net when you can just go round it?
Honourable mention
Shock of the day
Bulgarian Grigor Dimitrov, a semi-finalist last year, crashed out in five sets to Hungary's Marton Fucsovics.
Stat of the day
111-110 – Konta won one point more than Sorana Cirstea in her three-set defeat
Quote of the day
Fallen seeds
Women: Aryna Sabalenka (5), Johanna Konta (9), Garbine Muguruza (10)
Men: Grigor Dimitrov (14), Milos Raonic (25)
Up next
Cameron Norrie is first up against Spain's Alejandro Davidovich Fokina, while Dan Evans, tied at 1-1 with Frenchman Corentin Moutet, will play to a finish. Novak Djokovic takes on Jan-Lennard Struff in the first night match.
