Djokovic, roared on by a raucous Flushing Meadows crowd, cried into his towel during the third set, tears still in his eyes as he lined up on the baseline for the next game.
The adulation for the world No. 1 served as a stark contrast to the treatment of Russian Medvedev, who was forced to endure boos from the New York crowd as he served for championship point.
With Medvedev serving for his first major title at 40-15 in the third set, jeers could be heard amongst the din at the Arthur Ashe Stadium.
The 25-year-old proceeded to double fault, sparking jubilant roars among the New York crowd, but Medvedev swiftly collected himself to win the following point and secure the title.
“Wow, that was special,” Medvedev told CNN’s Carolyn Manno when asked about the partisan atmosphere.
“As soon as we went on the court, it was different to all the matches I played here before. You felt it was a special, special night, special evening, more for him and the crowd going for him and they tried so hard to get him on.
“They definitely didn’t want to disturb me on purpose, I doubt it, but of course before the second serve you get the screams, you make double fault, and the whole crowd goes crazy — it’s really tough.
“I know I have to focus on myself and how do I win this match, and again I managed to do it so that’s all that matters,” he added.
As he was continuously booed throughout his post-match interview, Medvedev waved his encouragement and told the crowd: “I won because of you.”
‘I’m sorry’: Medvedev feels for tearful Djokovic
Djokovic too has been on the end of jeers at the venue in the past, but there was only overwhelming love for the Serb this time round.
Six years ago during his triumph over Roger Federer, Djokovic found himself as the firm second favorite of the New York crowd, but was roared on throughout in his pursuit of a record 21st grand slam against Medvedev.
Sat in his chair at 5-4 in the third set, an immense swell of encouragement saw an emotional Djokovic shed tears as he covered his face with his towel before returning to the baseline.
“I said sorry to him,” Medvedev revealed to CNN when asked what he said to Djokovic at the net following his win.
“Tennis is such a brutal sport — there is two guys and one is going to lose no matter if it’s the first round or the final.
“I always watch Novak, Rafa [Nadal], Roger [Federer] play these finals and I feel like every time in the speech they’re sorry for their opponent because they know how it feels.
“I stopped Novak from doing something crazy and unbelievable in tennis history and I do feel sorry for him.
“I’m happy for myself but I do feel sorry for him, that’s what I said and yeah, Novak is such a great guy that he just said I deserve everything and he really hugged me and that’s unbelievable.”
‘Pure happiness’ for Medvedev
Boos aside, a superb victory marked a crowning achievement for Medvedev, made all the sweeter by the pain of the two grand slam final defeats that came before.
He was pipped to his first US Open final in an exhilarating five-set bout against Rafael Nadal two years ago, before suffering a straight-sets defeat to Djokovic at the Australian Open final in February.
Flipping the script in New York, Medvedev revealed he had doubts ahead of his first triumph.
“It’s pure happiness,” he told CNN.
“Being in two finals before, losing against Rafa and Novak, unbelievable players. Coming in this one, you always think: ‘Am I strong enough to be able to stop Novak from getting a calendar grand slam?’
“I was not playing my best but he destroyed me in Australia; I was not feeling good afterwards, confidence goes down a little bit.
“I’m just really happy that I managed to give my best today. I managed to win against one of the greatest of all time in straight sets in a match that meant everything to him … that’s special.”