See main article: 2001 US Open (tennis). Lleyton Hewitt defeated Pete Sampras in the final, 7–6(7–4), 6–1, 6–1 to win the men's singles tennis title at the 2001 US Open. It was his first major singles title.
Marat Safin was the defending champion, but lost in the semifinals to Sampras in a rematch of the previous year's final.
This was the last major appearance of former world No. 1 and two-time US Open champion Pat Rafter; he lost in the fourth round to Sampras. This was the first major main draw appearance of future Tour Finals champion David Nalbandian.
The high-profile quarterfinal match between Sampras and Andre Agassi was an all-time classic, and saw Sampras and Agassi each hold serve in every one of their 24 service games apiece. The match had no breaks of serve, and ended with Sampras winning 6–7(7–9), 7–6(7–2), 7–6(7–2), 7–6(7–5).
This was the first time the US Open used 32 seeds instead of 16, in order to better spread out the higher ranked players.
The seeded players are listed below. Lleyton Hewitt is the champion; others show the round in which they were eliminated.
See main article: 2001 US Open – Men's singles qualifying.