History was made at the 2021 US Open -- just not the kind of history many expected.
Djokovic, who sought to break a tie with Rafael Nadal and Roger Federer for most career men's Grand Slams, wasn't able to stop Medvedev's serve, as the 25-year-old recorded 16 aces en route to his first major title.
The women's championship made history of its own when unseeded qualifier Emma Raducanu of Great Britain beat unseeded Leylah Fernandez of Canada. It was the first time two unseeded players met in the final in the Open era and the first time a qualifier advanced to the championship, let alone won the event.
Here's all you need to know about this year's tournament.
US Open men's final: Medvedev stuns Djokovic
Daniil Medvedev stuns Novak Djokovic in straight sets. Read.
Aishwarya Kumar: Novak Djokovic felt 'relief' after bid for Grand Slam falls short. Read.
Social reaction: Medvedev earns praise from Andy Roddick, Eugenie Bouchard and other greats. Read.
US Open women's final: Raducanu tops Fernandez
Ohm Youngmisuk: How Emma Raducanu became women's tennis' newest, and perhaps most unlikely, major champion. Read.
D'Arcy Maine: Emma Raducanu's US Open victory brings cautious optimism for her future. Read.
Aishwarya Kumar: Leylah Fernandez extols New York's strength in wake of 9/11. Read.
Social reaction: Leylah Fernandez and Emma Raducanu's US Open Finals match had social media in awe. Read.
Ohm Youngmisuk: Novak Djokovic is just one win away from tennis' pinnacle. Read.
D'Arcy Maine: For Daniil Medvedev, nothing but a Slam title will do. Read.
Aishwarya Kumar: No matter who wins the title come Saturday, a new teenager will be crowned the US Open champion. And the tournament boasts a long list of teen champs who have gone on to have successful careers, the latest being Canada's Bianca Andreescu, who beat Serena Williams in 2019.Read.
Maine: Fernandez-Raducanu is a dream matchup ... and one no one was expecting it. Read.
Youngmisuk: An upset Garbine Muguruza let Barbora Krejcikova know that she thought the eighth-seeded Czech was "unprofessional" by taking a medical timeout just as the ninth-seeded Spaniard had the momentum in the second set of their fourth-round match at the US Open. Read.
Maine: Is it the maple syrup? Leylah Fernandez and Felix Auger-Aliassime are leading the Canadian resurgence at US Open. Read.
Kumar: Leylah Fernandez is "not surprised" by this memorable run to quarterfinals. Read.
Maine: Alcaraz was always supposed to be this good. But just not this soon. Read.
Experts' picks: Now in Week 2 of the US Open, what are our reporters thoughts? Djokovic is inching closer and closer to history, and with Ash Barty and Naomi Osaka out, who has the best shot on the women's side? Read.
Week 1 in review
Jerry Bembry: A message for Naomi Osaka -- take all the time you need. The four-time Grand Slam champion may need extended time out of the public eye. Read.
Kevin Van Valkenburg: Van Valkenburg made a vow to watch -- to truly watch -- Osaka move through time and space at the US Open. No questions, no quotes. He was just going to write what he saw. What he saw, he now realizes, was someone in pain. Read.
Maine: Drama has been aplenty at this year's US Open with Andy Murray calling out Stefanos Tsitsipas for taking a lengthy bathroom break. Read.
Maine: For longtime friends Sloane Stephens and Coco Gauff, US Open faceoff was a "full-circle moment." Read.
Kumar: Fans at Flushing Meadows were supposed to have had at least one dose of the COVID-19 vaccine as mandated on Aug. 27 by New York state. But one group didn't have to go through the same protocols: the players and their teams. Here's how players feel about it. Read.
Kumar: The rain came down heavy in New York and disrupted play at Louis Armstrong Stadium despite the retractable roof. Read.
Van Valkenburg: Nick Kyrgios did what he does best -- he turned a fairly benign match into a small spectacle. He cursed, he pouted, he feuded with the chair umpire over petty things. But he failed to advance past the first round. Read.
US Open previews
Simon Cambers: As Djokovic begins the final stage in his quest for the coveted Grand Slam, Laver will be as eager as anyone to see the world No. 1. Read.
Cambers: The absence of Federer and Nadal has opened up the US Open to the next generation of men's tennis. Read.
Bill Connelly: With his natural athleticism and defensive abilities, Djokovic was destined to become a top-flight tennis player. But he has become perhaps the greatest men's player ever because of his ability to turn the few relative weaknesses in his game into outright strengths. Read.
Experts' picks: If not Djokovic, who will win the men's singles title and why? Who will win the women's singles title and why? Our experts break down this year's tournament and what to expect from it. Read.
Maine: The players and storylines you won't want to miss heading into the tournament. Read.