
The top-seeded German ruthlessly snuffed out a late surge by Shelton to triumph 6-3, 7-6 (7/2), 5-7, 6-2, ending the eighth seed's bid to become the first US man in 23 years to win a Grand Slam title.
Zverev expunged the bitter memory of his 2020 US Open defeat, when he was two points from victory before falling to Dominic Thiem in five sets.
It would be six years -- with two major finals disappointments -- before he would break through this season.
"I think God has seen how hard we worked, how much we suffered, how much pain we went through and I think 2026 is the outcome of all the years that happened before," Zverev said at the trophy presentation.
The 23-year-old Shelton was one month shy of his first birthday when Andy Roddick hoisted the 2003 US Open trophy in the last major triumph for a US man.
Hopes were high that Shelton could end the drought after his epic five-set quarter-final victory over defending champion Carlos Alcaraz, and a come-from-behind win over compatriot Frances Tiafoe in the semi-finals.
But Zverev's all-court excellence proved too much for Shelton, despite the support of a star-studded Arthur Ashe Stadium crowd trying to will the American to victory.
With their backing, Shelton surged in the third set, eliminating the errors that Zverev had ruthlessly exploited.
Serving to extend the set, Zverev fell behind 0-40. Shelton fired long on his first set point but on the second Zverev's forehand volley went wide. Shelton had his first break of the match and they were headed to a fourth set.
Zverev, however, responded immediately and decisively.
He ran Shelton ragged through a 24-shot rally until Shelton sailed a backhand wide to drop his serve in the opening game of the fourth set.
He rolled home, lifting his arms in triumph after Shelton fired a serve return long on match point and finally receiving his own huge cheer from the crowd.
"I know that 99.9% of people wanted Ben to win, so I'm sorry," Zverev said at the trophy presentation. "It was an incredible atmosphere to play in."
If it seemed it took a moment for the win to sink in, Zverev said it was because he had lost track of the score.
"It was a long match, a long two weeks," he told ESPN.
Zverev had followed up his French Open victory with a runner-up finish at Wimbledon.
But his New York prospects had looked bleak as he labored through two five-setters to start the tournament.
Now the 29-year-old ranked second in the world has a chance to challenge for the number one ranking with Italian Jannik Sinner currently sidelined by a knee injury.