Zverev could not contain his emotions after the match with the German having squandered the opportunity to serve out for the title in the fifth set.
"I wish we could have two winners today".
Zverev has struggled to find anything like his best form for most of this tournament but swung freely and aggressively to take it to Thiem, who seemed nervous.
The Austrian not only won his first Grand Slam title, he did it from two sets down and became the first man after 71 years and first in Open Era to complete that kind of comeback at Flushing Meadows.
Kunieda, who first rose to world No.1 in 2007, now owns 24 Grand Slam singles titles.
Carried by this momentum, Thiem had a clear upper hand on the court in set number four, dropping two points behind the initial shot and creating two break chances in the sixth game.
"It's going to be or I expect that it's going to be easier for me now in the biggest tournaments", Thiem told reporters. It's wonderful how far our journey brought us to share this moment.
He fell as the first first-time Grand Slam champion since Marin Cilic at the 2014 U.S. Open, after six long, long years of unbroken rule from the royals.
It was the Austrian's fourth grand slam final after two losses to Rafael Nadal at the French Open and one to Novak Djokovic in Australia, and he admitted: "I was so tight in the beginning. I wish you would have missed a little bit more so I could have hold that trophy up", he added.
Zverev's debut appearance in the last-two of a tennis major came after he reached the semi-finals of the Australian Open earlier this year.
It was Thiem's first U.S. Open title. I think we were both ranked somewhere close to 100 or something, and there developed straightaway great friendship.
He also lost in the final of the French Open in 2018 and 2019, both times to Nadal. I want to thank my parents. I'm sure even though I lost they're pretty proud and I wish one day I can bring this trophy home.
Incredibly, Zverev broke back to send a dramatic match into a deciding set tie-break.
"For Thiem to get himself back into it, both mentally and physically, was fantastic". He forced a break point at 5-5 and then gratefully received two groundstroke errors from the wobbling Zverev, calling for treatment on his calf as he prepared to serve for his destiny.
At the moment of victory he collapsed to the court in elation and exhaustion before sharing a hug with a disconsolate but sporting Zverev.
Almost three hours were on the clock as they went into the decider, which Thiem began with a break that was quickly wiped out as Zverev stemmed his momentum.