2021 US Open – Men's singles
Daniil Medvedev defeated Novak Djokovic in the final, 6–4, 6–4, 6–4 to win the men's singles tennis title at the [2021 US Open (tennis)|US Open (tennis)|2021 US Open]. It was his first major title. Medvedev was the third Russian man, after Yevgeny Kafelnikov and Marat Safin, to win a major singles title.
Dominic Thiem was the reigning champion, but did not participate due to an ongoing wrist injury. This wrist injury would eventually lead to his retirement from the sport in 2024.
Djokovic was aiming to become the second man in the Open Era, after Rod Laver in 1969, to complete the Grand Slam. He was also attempting to win an outright record 21st major singles title and surpass his Big Three counterparts, Roger Federer and Rafael Nadal. By reaching the final, Djokovic tied Federer's record of 31 men's singles major finals contested, and repeated his 2015 achievement of reaching all four major finals in a season. This marked Djokovic's sixth runner-up finish at the event, the most at a men's singles major and ATP Tour event overall.
By defeating world No. 3 Stefanos Tsitsipas in the third round, Carlos Alcaraz became the youngest man to beat a top 3 ranked-player in singles at the US Open since the inception of the ATP rankings in 1973. He was the youngest male quarterfinalist at a singles major since Michael Chang at the 1989 French Open, and the youngest at the US Open in the Open Era; he would win the title the following year. Botic van de Zandschulp was the first Dutchman to reach a singles major quarterfinal since Sjeng Schalken at the 2004 Wimbledon Championships and the first qualifier to do so at the US Open since Gilles Müller in 2008.
Seeded players
The following are the seeded players. Seedings are based on ATP rankings as of August 23, 2021. Rank and points before are as of August 30, 2021.As a result of pandemic-related adjustments to the ranking system, players are defending the greater of their points from the 2019 and 2020 tournaments.
| Seed | Rank | Player | Points before | Points defending from 2019 or 2020 | Points won | Points after | Status | |||
| 1 | 1 |  Withdrawn playersThe following players would have been seeded, but withdrew before the tournament began.
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