Medvedev, the 2021 champion in New York, outclassed Nuno Borges, who was bidding to become the first Portuguese man to make a Grand Slam quarter-final, 6-0, 6-1, 6-3.
Top seed Sinner, who won his maiden Slam at the Australian Open this year, takes on Tommy Paul in the night session on Arthur Ashe Stadium.
French Open champion and women's world number one Iga Swiatek, meanwhile, hopes to take another step closer to a second US Open title when the 2022 winner faces Liudmila Samsonova of Russia.
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