The British number two lost to 18-year-old Spaniard Carlos Alcaraz.
Norrie has enjoyed such a successful 2021 that he was seeded 26 フラッシングメドウズで.
The 26-year-old had also reached the third round in his previous four grand slams events.
But he was beaten in straight sets by US Open debutant Alcaraz, で 18 the youngest man in the world’s top 100.
Norrie had no answer to the youngster’s powerful hitting as he went down 6-4 6-4 6-3.