| Champ: |  Daniil Medvedev |
| Runner: |  Novak Djokovic |
| Score: | 6–4, 6–4, 6–4 |
| Draw: | 128 (16 / 8) |
| Seeds: | 32 |
See main article: 2021 US Open (tennis).
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.[1] It was his first major title. Medvedev became the third Russian man, after Yevgeny Kafelnikov and Marat Safin, to win a major singles title, and the first to do so since Safin at the 2005 Australian Open. He lost just one set during the tournament, against Botic van de Zandschulp in the quarterfinals. Djokovic was aiming to become the second man in the Open Era, after Rod Laver in 1969, to complete the Grand Slam.[2] 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 contesting the maximum-possible 28 major singles matches in a season. This marked Djokovic's record sixth runner-up finish at the event.
Dominic Thiem was the reigning champion, but did not participate due to an ongoing wrist injury.[3]
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 became 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 go on to win the title the following year.[4] Van de Zandschulp became 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.[5] [6]
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 | Novak Djokovic | 11,113 | 180 | 1,200 | 12,133 | Runner-up, lost to Daniil Medvedev [2] | |
| 2 | 2 | Daniil Medvedev | 9,980 | 1,200 | 2,000 | 10,780 | Champion, defeated Novak Djokovic [1] | |
| 3 | 3 | Stefanos Tsitsipas | 8,350 | (150)† | 90 | 8,350^ | Third round lost to  Carlos Alcaraz | |
| 4 | 4 | 8,240 | 1,200 | 720 | 7,760 | Semifinals lost to Novak Djokovic [1] | ||
| 5 | 7 | 6,400 | 360 | 90 | 6,130 | Third round lost to  Frances Tiafoe | ||
| 6 | 8 | 5,533 | 720 | 360 | 5,173 | Quarterfinals lost to Novak Djokovic [1] | ||
| 7 | 10 |  Denis Shapovalov | 3,580 | 360 | 90 | 3,310 | ||
| 8 | 11 |  Casper Ruud | 3,455 | 90 | 45 | 3,440^ | Second round lost to Botic van de Zandschulp [Q] | |
| 9 | 12 | Pablo Carreño Busta | 3,325 | 720 | 10 | 2,650^ | First round lost to Maxime Cressy [Q] | |
| 10 | 13 |  Hubert Hurkacz | 3,128 | 45 | 45 | 3,128 | Second round lost to  Andreas Seppi | |
| 11 | 14 |  Diego Schwartzman | 2,980 | 360 | 180 | 2,800 | Fourth round lost to Botic van de Zandschulp [Q] | |
| 12 | 15 | Félix Auger-Aliassime | 2,828 | 180 | 720 | 3,368 | Semifinals lost to Daniil Medvedev [2] | |
| 13 | 16 | Jannik Sinner | 2,750 | 35 | 180 | 2,895 | Fourth round lost to Alexander Zverev [4] | |
| 14 | 17 |  Alex de Minaur | 2,555 | 360 | 10 | 2,218^ | ||
| 15 | 18 | 2,511 | 720 | 45 | 1,836 | Second round retired against Alexei Popyrin | ||
| 16 | 19 | Cristian Garín | 2,510 | 45 | 45 | 2,510 | Second round lost to Henri Laaksonen [Q] | |
| 17 | 20 | 2,503 | 360 | 90 | 2,233 | Third round lost to Jannik Sinner [13] | ||
| 18 | 21 | Roberto Bautista Agut | 2,405 | 90 | 90 | 2,405 | Third round lost to Félix Auger-Aliassime [12] | |
| 19 | 22 | 2,238 | 90 | 10 | 2,171^ | First round lost to Brandon Nakashima [WC] | ||
| 20 | 23 | 2,227 | 45+125‡ | 10+20 | 2,097^ | First round lost to Oscar Otte [Q] | ||
| 21 | 25 | 2,109 | (125)§ | 90 | 2,074 | Third round lost to Jenson Brooksby [WC] | ||
| 22 | 24 | 2,206 | 45 | 180 | 2,341 | Fourth round lost to Lloyd Harris | ||
| 23 | 26 | 2,090 | 45+90‡ | 10+45 | 2,045^ | First round lost to Peter Gojowczyk [Q] | ||
| 24 | 27 | 2,074 | 90 | 180 | 2,164 | Fourth round lost to Daniil Medvedev [2] | ||
| 25 | 28 | 2,010 | 90 | 10 | 1,965^ | |||
| 26 | 29 | 1,975 | 90 | 10 | 1,930^ | First round lost to Carlos Alcaraz | ||
| 27 | 30 |  David Goffin | 1,933 | 180 | 10 | 1,766^ | First round lost to Mackenzie McDonald | |
| 28 | 31 | Fabio Fognini | 1,734 | 10 | 10 | 1,744^ | ||
| 29 | 32 | 1,723 | 180+194‡ | 10+60 | 1,429^ | First round lost to Marco Trungelliti [Q] | ||
| 30 | 36 | 1,650 | 180 | 10 | 1,493^ | First round retired against Philipp Kohlschreiber [PR] | ||
| 31 | 37 | 1,633 | 90 | 45 | 1,588 | Second round lost to Jack Sock [WC] | ||
| 32 | 38 | Filip Krajinović | 1,589 | 90 | 10 | 1,544^ | First round lost to Guido Pella |
The following players would have been seeded, but withdrew before the tournament began.
| Rank | Player | Points before | Points defending from 2019 or 2020 | Points after | Withdrawal reason | |
|---|---|---|---|---|---|---|
| 5 | Rafael Nadal | 7,815 | 2,000 | 5,815 | Left foot Injury | |
| 6 |  Dominic Thiem | 6,995 | 2,000 | 4,995 | Right wrist injury | |
| 9 | Roger Federer | 4,125 | 360 | 3,765 | Right knee surgery | |
| 33 | Stan Wawrinka | 1,715 < | --After 2020 Prague Challenger II points are dropped--> | 360 | 1,355 | Left foot injury |
| 34 | 1,694 | 45 | 1,649 | Right leg injury | ||
| 35 | Borna Ćorić | 1,674 | 360 | 1,319^ | Right shoulder injury |
See also: 2021 US Open – Men's singles qualifying.