Top seeded Djokovic, the 2011 champion, wrapped up a place in his 18th successive Grand Slam quarterfinal when he crushed Spanish world number 43 Marcel Granollers 6-3, 6-0, 6-0 in just 79 minutes. (Agencies)
Andy Murray, the third seed, reached the quarter-finals for a third successive year with a 6-7 (5/7), 6-1, 6-4, 6-4 win over Denis Istomin, the 64th-ranked Uzbek.
Djokovic will next tackle Russian 21st seed Mikhail Youzhny, a semi-finalist in 2006 and 2010, over whom he has an 5-3 career lead.
Youzhny carved out a four-hour, 6-3, 3-6, 6-7 (3/7), 6-4, 7-5 win over 2001 champion Lleyon Hewitt after trailing 4-1 in the fourth set and 5-2 in the fifth.
Swiss ninth seed Stanislas Wawrinka reached the last eight by eliminating Czech fifth seed Tomas Berdych, a semi-finalist last year, 3-6, 6-1, 7-6 (8/6), 6-2.
Wawrinka will now face Murray for a place in the last four, trailing 8-5 in their series, although he did win their 2010 US Open third-round meeting.
Djokovic, bidding to make the final for a fourth successive year, hit 34 winners and faced just one break point against Granollers, one of four Spaniards in the last 16.
But Granollers' challenge had already been fatally undermined by having played three five-set matches and spending almost 10 hours on court, twice as long as Djokovic, who has yet to lose a set.
"I definitely played one of the best matches that I've played in my life here at the Arthur Ashe Stadium," Djokovic said after winning the last 15 games of the one-sided tie.
"It was 3-all in the first set and then I managed to get the right advantage and I played flawless tennis," he said.
He also won the first 25 points in a row on his serve to start the match.
"This is probably the first time I've experienced something like that. I can't say I have one of the strongest serves on the tour but I served pretty well," Djokovic said.
Top seeded Djokovic, the 2011 champion, wrapped up a place in his 18th successive Grand Slam quarterfinal when he crushed Spanish world number 43 Marcel Granollers 6-3, 6-0, 6-0 in just 79 minutes.