Djokovic has reached the final at Flushing Meadows in each of the last four years and remains on course to do so again following a straightforward 6-3 6-2 6-2 win on Saturday.
In the ninth meeting between Djokovic and the American world number 57, the Wimbledon champion made a flying start.
Breaking twice early on, the world number one found himself 5-0 to the good after just 15 minutes - losing only nine points in the process.
While Querrey recovered to win the next three games, it was not enough as Djokovic held firm to see out the opening set.
A first-serve percentage of 80 per cent in the second set helped the 2011 US Open champion continue his dominance as the 27-year-old went 6-3 6-2 ahead in less than an hour.
Querrey - who made the semi-final in Winston-Salem earlier this month - offered some resistance in the final set as he produced four aces.
However, Djokovic broke twice more before winning the second of two match points to wrap up victory.
Fifth seed Milos Raonic is also safely into the fourth round after edging past Victor Estrella Burgos in a hard-fought clash.
The Canadian ran out 7-5 (7-5) 7-6 (7-5) 7-6 (7-3) against the world number 80 from the Dominican Republic.