Second seed Nadal got past fifth seed Medvedev 7–5, 6–3, 5–7, 4–6, 6–4, with the Russian showing great fight to respond from two sets down in a match which almost lasted five hours.
The triumph is Nadal’s fourth title at Flushing Meadows and adds to his French Open crown from earlier this year.
The victory also moves the Spaniard within one major title of Roger Federer’s record of 20.
“I cannot be all the time thinking about more and more. I just try to do it my way,” Nadal said.
“I’m more than happy about the career I have.
“I can’t be frustrated if the guys are doing a little bit better than me.
“Let’s see what goes on in the next couple of years.”
The match lasted exactly four hours and 50 minutes, full of twists and turns.
“It was a dramatic match. The match had everything,” Nadal said.
“Medvedev is one of the toughest competitors and one of the best players in the world.”
The 33-year-old praised Medvedev, 23, who pushed him all the way.
“It means a lot to me to have this trophy in my hands,” the Spaniard said.
“I resisted well during the last three hours of the match. He played amazing.”