The Italian has won three of the past four majors, having followed last year’s US Open success with victories at January’s Australian Open and at Wimbledon last month.
Sinner’s only Grand Slam loss so far this year was to Spaniard Alcaraz in an epic French Open final in June.
“I have amazing memories,” said Sinner, when asked about returning to Flushing Meadows as defending champion.
“Every year is different and you come here starting this tournament hopefully in the best possible way, which I have done.
“Coming back to a Grand Slam, where the emotions are still running – I’m very happy to come back here and compete against the best players in the world.”
Sinner’s second-round opponent will be Australia’s world number 36 Alexei Popyrin, who defeated Emil Ruusuvuori of Finland in straight sets.