Serbia's world No 1 defeated Kohlschreiber 6-1 7-5 6-4 on another muggy day at Flushing Meadows, reaching the last eight at the US Open for the eighth straight year.
It's his 22nd successive Grand Slam quarter-final, a run that stretches back to Kohlschreiber's victory over him in the third round of the 2009 French Open.
The Wimbledon champion looked headed for a short day's work when he raced through the first set in 25 minutes.
Djokovic did so with a stinging forehand passing shot to end a rally that sent the Louis Armstrong Stadium crowd wild, then broke Kohlschreiber for a 6-5 lead.
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Djokovic will play either eighth-seeded Andy Murray or ninth-seeded Jo-Wilfried Tsonga for a semi-final berth. Murray and Tsonga renewed an old rivalry in which the Scot has won nine of their 11 career meetings.