The meeting took place at the Arthur Ash Stadium in New York, lasted 2 hours 16 minutes and ended with a score of 6: 4, 6: 4, 6: 4 in favor of the 25-year-old Russian.
He made 15 innings through the game, made five double faults and converted four break points.
The prize fund of the tournament was $ 57.5 million.
For a domestic athlete, this is the second final at the US Open and for the first time he won.
The Serb is a 20-time Grand Slam champion, and he won the American Major three times.
Earlier it was reported that Medvedev made two double mistakes after fans prevented him from filing for a match-bole.