Khachanov, ranked 50th in the world, downed Auger-Aliassime 6-7 (5/7), 6-3, 6-2, 6-2, pulling away relentlessly as the Canadian struggled with “abnormal” physical issues.
“It’s tough to talk about anything other than how I felt physically,” a dejected Auger-Aliassime said, adding that he was “dizzy and seeing spots and couldn’t recover”.
“I thought maybe it would pass, but it didn’t.”
Khachanov took full advantage of 47 unforced errors, with eight double faults, from Auger-Aliassime, who struggled particularly on serve.
“I thought maybe he had some physical issues, it’s part of our sport,” Khachanov said. “From my side I tried to give my best performance, fighting, fighting.
“I’m super happy to get this win,” added the 2022 semi-finalist after posting his first top-10 win of the year.
It was the second big upset on the men’s side, after an ailing Novak Djokovic was ousted in the first round, and further opened up a men’s field headed by world number two Alexander Zverev.
French Open champion Zverev, who battled through five sets to beat Lorenzo Sonego in the first round, anchors the night session on Arthur Ashe Stadium, taking on 52nd-ranked Frenchman Quentin Halys for a place in the third round.
Two former champions booked their third-round berths, Iga Swiatek marching through with a 6-3, 6-2 victory over Nadia Podroska while Naomi Osaka survived a second-set swoon to beat Katerina Siniakova 6-2, 5-7, 6-1.
Swiatek, whose six Grand Slam titles include the 2022 US Open, had things mostly her own way against the former top-40 player now sunk to 449th in the world.
She fought off four break points at 5-3 in the first set then pulled away with two breaks for a 5-1 lead in the second, polishing off the win in an hour and 11 minutes.
It was another encouraging performance for the former world number one, who hadn’t reached a final in 2026 until her run to the title at Toronto in August.
“I’m here with better feeling than any other Grand Slam this year,” Swiatek said. “Just trying to enjoy every day and improve the game every day.”
Japan’s Osaka, who counts two US Open titles among her four major trophies, looked in total control against Siniakova as she raced through the first set and to a 4-2 lead in the second without facing a break point.
But the Japanese star’s unforced errors began to pile up – 20 in the second set compared to four in the first – and doubles world number one Siniakova pounced to climb from 5-3 down and take the set.
Osaka gave herself a talking to during a bathroom break and regrouped in the decider, riding a quick break to a 3-0 lead and fending off a pair of break points in the fifth game on the way to the win.
“I just felt like I had to fight,” she said.
So did former Australian Open champion Madison Keys, who saved five match points as she rallied from 5-2 down in the third set to beat Anna Bondar 4-7, 6-4, 7-6 (10/5).
In other early matches, 2025 runner-up Amanda Anisimova advanced with a 6-3, 3-6, 6-1 victory over Austrian Lilli Tagger, and rising Philippines star Alexandra Eala beat Oleksandra Oliynykova 6-1, 6-4.
Coco Gauff, another former US Open champion, opens the night session on Ashe against former world number two Paula Badosa.
The Spaniard leads their head-to-head, including a victory over Gauff in Berlin this year.
Generations collide on Louis Armstrong Stadium when 40-year-old Gael Monfils takes on 20-year old American Learner Tien.
Monfils, trying to extend the final Grand Slam of his career before he heads into retirement, fell to Tien at Cincinnati in August in their only meeting to date.
In other marquee matches, reigning Australian Open champion Elena Rybakina takes on Spain’s Jessica Bouzas and French Open winner Mirra Andreeva plays Eva Lys. (AFP)