Sinner has lost only two hard-court matches this season and won four titles on the surface, including his first Grand Slam triumph at January’s Australian Open.
His most recent success was at Cincinnati in August, winning the title the day before news emerged he had been cleared of any wrongdoing after twice testing positive for a banned substance earlier this year.
Sinner looked close to his best against O’Connell, firing down 46 winners and 15 aces, while he denied the world number 87 any break points across the three sets.
With Djokovic and Alcaraz – the last two champions in New York – out of the tournament, the door has been left ajar for the likes of Sinner and Medvedev.
Medvedev, the winner of the 2021 US Open, showed resilience to come out on top of a topsy-turvy first set against Cobolli.
Having broke early and held firm on serve to win the second, Medvedev, who is often known for being hot-headed on court kept his cool in a back-and-forth third-set tussle and emerged triumphant after breaking for the fourth time.
The 28-year-old will continue his bid for a second Grand Slam title against Nuno Borges of Portugal, who clinched a stunning 6-7 (5-7) 6-1 3-6 7-6 (8-6) 6-0 comeback win against 18-year-old Czech Jakub Mensik.
“If I play good tennis I can win the whole thing,” Medvedev said. “If I don’t play good I can lose against anyone. I just have to play my best and try to win.”
Elsewhere, Australia’s Jordan Thompson booked his spot in a Grand Slam last 16 for just the second time in his career as he moved past Italian 30th seed Matteo Arnaldi 7-5 6-2 7-6 (7-5).
