World number one and top seed Djokovic defeated 79th-ranked Schwartzman 6-1, 6-2, 6-4, wrapping up the marquee match on Arthur Ashe Stadium court minutes before midnight.
"I hope it was a midnight delight," the reigning Wimbledon champion told fans, although in truth the contest offered little drama.
Schwartzman, playing just his second Grand Slam tournament and his first tour-level hardcourt event, pulled the Serbian star into rallies from the baseline, even breaking him for his only game of the opening set.
Trailing 2-3 in the third, Schwartzman broke Djokovic to knot the set at 3-3, but Djokovic, seeking to add a second US Open title to the one he captured in 2011, promptly broke him at love for a 4-3 lead and sealed the victory on his second match point with a shot that clipped the net and fell his way.
"I thought I hit the ball very well throughout the whole match," Djokovic said. "I'm very pleased. It's never easy to start a US Open smoothly."
That was the common refrain on the opening day, as former champions Andy Murray, Maria Sharapova and Venus Williams also advanced, taking center stage with two-time defending champion Serena Williams and five-time champion Roger Federer due to launch their campaigns on Tuesday.
Murray lumbered through a 6-3, 7-6 (8/6), 1-6, 7-5 victory over 70th-ranked Dutchman Robin Haase, battling painful muscle cramps that struck without warning.
"I could have easily lost that match," said Murray, who thought he'd have been in real trouble in a fifth set. "I was very close to losing the match."
Murray twice fought back from a break down in the fourth -- Haase unable to press his advantage at 4-1 and again at 5-3 even as Murray could be seen clutching various areas of his body on shot after shot.
"I don't know exactly why it happened today," said Murray, who trains in the steamy heat of Miami and didn't think the 30 C temperatures on Louis Armstrong Stadium were excessive. "At the time it happened I wasn't exhausted."
Murray finally gained the decisive break for a 6-5 lead and finished off the match after just over three hours.
- US Open goosebumps -
Fifth-seeded Sharapova, who lifted the trophy in 2006, rallied with a vengeance from an early break against fellow Russian Maria Kirilenko.
Trailing 2-4, Sharapova won the next 10 games to take the match.
"It's always tough to start here in New York," said French Open champion Sharapova, who was just happy to be back under the lights on Ashe after missing last year's edition with a season-ending shoulder injury.
"You feel the goosebumps when you go out in a night match on Ashe," Sharapova said.
Venus Williams, the winner in 2000 and 2001, punched her second-rund ticket with a 2-6, 6-3, 6-3 win over Japanese veteran Kimiko Date Krumm.
Other notable names in action included Australian Open champion Stan Wawrinka, the men's third seed who defeated Czech Jiri Vesely 6-2, 7-6 (8/6), 7-6 (7/3).
Big-serving Canadian Milos Raonic, the fifth seed, pelted Japanese qualifier Taro Daniel with 20 aces in a 6-3, 6-2, 7-6 (7/1) victory.
Women's second seed Simona Halep shook off first-round jitters to defeat unranked US wildcard Danielle Collins 6-7 (2/7), 6-1, 6-2.
Romania's Halep, who has quietly risen to number two in the world, admitted she was a bit intimidated to find herself the first match of the tournament on the imposing Ashe court.
"It's not easy to manage the situation, but I think after first set did I very well," said the 22-year-old who was runner up to Sharapova at Roland Garros.
Agnieszka Radwanska showed no sign of big-tournament nerves, but the fourth-seeded Pole said she felt them nonetheless in a 6-1, 6-0 drubbing of Canadian Sharon Fichman.
"First match is always tricky," Radwanska said.