Nadal, a 12-time Grand Slam champion who has won nine titles since returning in February from a seven-month injury layoff, stretched a career-best hardcourt win streak to 18 matches by beating Croatian Ivan Dodig, 6-4, 6-3, 6-3 yesterday.
"I started the match with the right intensity," Nadal said. "I think I played my best match of the week so far."
Second-seeded Spaniard Nadal, who completed a career Grand Slam with his 2010 US Open crown, and Swiss star Roger Federer, in his lowest Grand Slam seeding since 2002 at seventh, have never played at the US Open but could meet in the quarter-finals.
Nadal, who has not lost his serve in three matches, took command early and connected on 65 percent of his first serves and fired 37 winners in improving to 56-3 this year.
"I have to improve a little bit of everything to keep going in the second week," Nadal said. "To win matches if you are not playing your best, it's impossible."
Next for Nadal, who missed last year's Open due to injured knees, will be German 22nd seed Philipp Kohlschreiber, who ousted US 13th seed John Isner.