Second seed Djokovic will tackle either Ukrainian 14th seed Alexander Dolgopolov or Swiss 18th seed Stanislas Wawrinka for a place in the quarter-finals.
Five-time champion Roger Federer defied 32-degree heat and crushing humidity to reach the last 16 on Saturday as potential semi-final rival Andy Murray almost wilted in the New York sweatshop.
Novak Djokovic returns to Julien Benneteau during a Rd 3 tie yesterday. Pic/AFP
Top seed Federer, bidding to be the first six-time winner in 87 years, defeated Spanish 25th seed Fernando Verdasco 6-3, 6-4, 6-4 in a shade over two hours to make the last 16 for the 12th successive year.
The Swiss next faces American 23rd seed Mardy Fish, who beat Gilles Simon, the French 16th seed, 6-1, 5-7, 7-6 (7/5), 6-3.
In stark contrast, third-seeded Murray, the 2008 US Open runner-up to Federer, needed almost four hours to clinch a
7-6 (7/5), 7-6 (7/5), 4-6, 7-6 (7/4) victory over 30th-seeded Spanish left-hander Feliciano Lopez. Olympic champion Murray will next face 15th-seeded Milos Raonic, who defeated American wildcard James Blake and 6-3, 6-0, 7-6 (7/3) on the back of 29 aces to become the first Canadian to make the last 16 in 24 years.
Murray, four times a Grand Slam runner-up, had lost only one set in six prior matches against Lopez but had to come back from trailing in all three tie-breakers on Saturday.
Federer only faced one break point against Verdasco, a player he has now defeated five times in five meetings.