Nadal will face five-time U.S. Open champion Federer for the first time in New York if the Swiss star defeats the 24th-seeded Juan Martin del Potro of Argentina in Wednesday night's other quarterfinals match. Del Potro won the U.S. Open in 2009.
The 31-year-old Nadal, who is a two-time winner in New York, got the early jump on the first-time major quarterfinalist Rublev, battering his young foe to claim the first two sets in a tidy 58 minutes.
"It was a good match," Nadal said in his on-court interview. "Andrey was playing in his first quarterfinal and he played with more mistakes than usual. It's an important victory for me, winning past two matches in straight sets is very good news for me.
"I'm very, very happy to be in the semifinals again in New York. It's very important to me and I'm very excited to have this opportunity again."
Nada converted seven of the 18 break points he created and won 84 percent of points behind his first serve.
The 53rd-ranked Rublev, who admitted that Nadal was his idol, was the youngest U.S. Open quarterfinalist since Andy Roddick in 2001.