Unseeded Russian veteran Karen Khachanov won 3-1 in sets in the second round.
"He might have had some physical problems," Khachanov said in the on-court interview.
Auger-Aliassime, who has reached the US Open semifinals twice and earlier this year made the quarterfinals of both the French Open and Wimbledon, has recently been struggling with back problems. He made 47 unforced errors in the match.
The 24-time Grand Slam winner Novak Djokovic, seeded fourth in the tournament, was eliminated in the first round.
Top-seeded German Alexander Zverev plays his second-round match on Friday night.
What do you think?