Defending champion Roger Federer defeated Andre Agassi in the final, 6–3, 2–6, 7–6(7–1), 6–1 to win the men's singles tennis title at the 2005 US Open.

This was the first US Open in which future champions Novak Djokovic, Andy Murray and Stan Wawrinka competed in the main draw.

Noteworthy in this tournament was a strong performance by American men, despite 2003 champion and former world No.

In addition to two-time US Open champion Agassi, wildcard James Blake reached the quarterfinals, upsetting world No.

This tournament marked the last major appearance of French Open champion Albert Costa.