Medvedev, playing in his third major final, at last hoisted a Grand Slam trophy while avenging a straight sets defeat by Djokovic earlier this year in the Australian Open final.
Emma Raducanu has become the youngest Grand Slam champion in 17 years, ending the tournament as the first player since Serena Williams in 2014 to not drop a set in the US Open.
One more victory will give the 34-year-old Djokovic the first calendar-year Slam since Rod Laver accomplished it 52 years ago.
Emma Raducanu, an 18-year-old from Britain who is ranked 150th, and Leykah Fernandez, a 19-year-old from Canada who is ranked 73rd, will clash in first Grand Slam final between teens since 1999.
World number one Ash Barty crashes out of US Open, losing 6-2 1-6 7-6(5) to 43rd-ranked American Shelby Rogers, in biggest upset of tournament thus far.
Naomi Osaka overcame a slow start to beat Czech Marie Bouzkova 6-4, 6-1 and get her US Open title defence under way in front of a roaring capacity crowd.
Serena Williams has had an injury-marred season and limped out of her first-round match at Wimbledon in tears due to the leg injury.
Medvedev will face fellow Russian Andrey Rublev in Saturday's semifinals after beating Pablo Carreno Busta.
Osaka, who has a Haitian father and Japanese mother, said she plans to do more In addition to donating prize money from the Western & Southern Open tennis tournament to relief efforts in Haiti, where a 7.2 magnitude quake killed over 1400.
World number-two ranked Daniil Medvedev of Russia beat John Isner of the United States 6-2, 6-2 in the National Bank Open semifinals to face American Reilly Opelka in the final.
Daniil Medvedev, ranked second in the world, has 11 ATP Tour victories, winning this year in Mallorca and Marseille. Meanwhile, Stefanos Tsitsipas ended the 13-match win streak of Casper Ruud with a clinical 6-1, 6-4 win to also reach the semis.
World number one Novak Djokovic admits that his exertions in Japan have taken their toll after pulling out of the Tokyo Olympics due to a shoulder injury.
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