Frances Tiafoe sealed the title for Team World with victory over Stefanos Tsitsipas.
Federer, who won 20 major singles titles, played Nadal 40 times in one of the most compelling rivalries across any sport.
In front of a 17,500 sell-out crowd in London, 20-time Grand Slam champion Federer returned from more than a year away for a last dance in tandem with his great rival on a gripping and memorable finale by the Thames.
The iconic duo will join forces at the Laver Cup on Friday.
The iconic player made his announcement via a lengthy social media post.
Zverev has not played since June after undergoing surgery to fix damaged ankle ligaments following an injury he suffered during his French Open semifinal.
Not since Andy Roddick in 2003 has a US man won the title at Flushing Meadows and the pressure was on for the 24-year-old Frances Tiafoe to build on his stunning win over second seed Rafa Nadal in the fourth round.
While Tiafoe played sublime tennis, he also benefited from an uncharacteristically poor serving and returning performance from Nadal. The Spaniard produced nine double faults and hit just 33 winners to Tiafoe's 48.
World No. 1 Iga Swiatek was made to work by American Lauren Davis before sealing a 6-3, 6-4 win to reach the fourth round at New York for the second straight year.
Nadal overcame a horrid start and a bloody nose to beat Fognini and reach the third round.