The German star, who had finished a five-set first round battle in the early hours of Wednesday morning, was again forced to go the distance before grinding out a 6-4, 4-6, 7-6(3), 6-7(3), 6-3 victory over France's Quentin Halys.
The 4hr 33 min slugfest was another gruelling outing on the Arthur Ashe Stadium show court for Zverev, who clinched victory at just after 2.15am local time.
The 29-year-old, who has spent nearly 10 hours on court in his opening two matches, will face Chile's Alejandro Tabilo in the next round.
"The performance was quite sh*t to be honest, but I won, that's the most important thing," Zverev said in an on-court interview afterwards.
"Another four-and-a-half hours, 2:15 am, that's what I go to the gym for," he added, before thanking die-hard fans who remained in the stadium for the end of the match.
"The couple thousand people (who stayed) made up for the 15,000 that left," he said.
Zverev had looked in complete control against Halys early on, seizing the only break of the first set to go 5-4 before holding to claim the opening frame.
The second set appeared to be following a similar pattern when Zverev earned the first break point for a chance to take a 5-4 lead again.
This time, though, Halys rallied and recovered to hold, leaving Zverev needing to hold to keep the set alive.
Yet Zverev's composed service game suddenly looked vulnerable and a double fault gave Halys two set points at 15-40 which the Frenchman pounced on to knot it at one set apiece.
Zverev recovered from a 4-1 deficit in the third set to level at 4-4.
Halys saved three break points to edge into a 5-4 lead and the rest of the set went on serve until the tiebreak, where Zverev was soon in charge, sprinting into a 5-1 lead before taking the set.
Yet it was a different story when the fourth set ended in a tiebreak, with Halys dominating Zverev to level the match and take send it to a decider.
With tension mounting, it was Halys who blinked first in the fifth set, slashing a forehand well wide to set up a crucial break for Zverev.
The German held twice to take a 5-3 lead and then broke a weary Halys to clinch victory.
