Zverev arrived in New York as a major champion for the first time after his French Open triumph in June and is widely seen as the man to beat with world number one Jannik Sinner absent and defending champion Carlos Alcaraz recently returning from injury.
Zverev converted only one of seven break-point opportunities in winning the opening set before world number 89 Sonego responded in the second, breaking early and shifting the momentum before serving out to love and sealing the set with an ace.
A back-and-forth third set went to a tiebreak, where a double fault from Zverev handed Sonego the opening he needed to move ahead 2-1.
After the pair traded breaks in the fourth, Zverev found himself two points away from defeat before securing a crucial hold and breaking serve to force a deciding set.
Zverev completed the turnaround as Sonego ran out of steam, the German happy to avoid becoming the first top seed to lose in the first round of a Grand Slam since Lleyton Hewitt in 2003 at Wimbledon.
"I'm just happy I won, that's it," Zverev said.
"I think it was an incredible battle, lots of ups and downs, nearly five hours. I think it was my longest first-round match at a Grand Slam.
"He would have beaten a lot of players but I'm happy to be through.
"I'm happy I won this kind of battle and it was exactly what I needed ... good things happen after you fight through these matches."
Zverev will next face Frenchman Quentin Halys.
US Open 2026
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