Dominic Thiem comfortably progressed to the US Open third round, beating India's Sumit Nagal 6-3 6-3 6-2.
The Austrian second seed, celebrating his 27th birthday, will next face 2014 champion Marin Cilic, who overcame Norbert Gombos 6-3 1-6 7-6 (7-2) 7-5.
There was a surprise as Vasek Pospisil knocked out fellow Canadian Milos Raonic 6-7 (1-7) 6-3 7-6 (7-4) 6-3.
Raonic, the 2016 Wimbledon finalist and seeded 24th, defeated Andy Murray at last week's Western and Southern Open.
World number 94 Pospisil will now play Spanish eighth seed Roberto Bautista Agut, who defeated Serb Miomir Kecmanovic 6-3 3-6 6-3 6-4 at Flushing Meadows.
Grigor Dimitrov, who reached the semi-finals in New York last year, lost 6-7 (5-7) 7-6 (7-4) 3-6 6-4 6-1 to Hungary's Marton Fucsovics.
Fucsovics next faces American Frances Tiafoe who beat Australia's John Millman 7-6 (8-6) 3-6 1-6 6-3 6-3.
Italian sixth seed Matteo Berrettini moved past Frenchman Ugo Humbert 6-4 6-4 7-6 (8-6) and will play Norway's 30th seed Casper Ruud.