Djokovic beat Czech qualifier Radek Stepanek 6-2 6-4 in a friendly encounter, during which both players repeatedly hammed it up for the crowd.
Stepanek, at 37 the oldest player in the field, broke serve in the first game of the second set but it was merely a stay of execution against the world number one from Serbia.
Djokovic is the only member of the so-called "big four" competing in Toronto, with last year's champion Andy Murray, Roger Federer and Rafa Nadal all absent from the $4.7 million event.
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In a tournament so far devoid of major upsets, the top five seeds advanced to the quarters, with Swiss Stan Wawrinka, Japanese Kei Nishikori, Canadian Milos Raonic and Czech Tomas Berdych booking last eight berths.
Only Berdych needed three sets to progress and the fifth seed's reward is a showdown against Djokovic, who leads their head-to-head by a staggering 24-2 margin.
Wawrinka won a hard-hitting battle with American Jack Sock, 7-6(3) 6-2.
Next up for the two-times grand slam champion is unseeded South African Kevin Anderson, who rallied for a 4-6 6-3 6-4 victory over the 12th seeded Australian Bernard Tomic.
Nishikori had little trouble getting by American Rajeev Ram, requiring just 68 minutes to register a convincing 6-3 6-4 win.
"The first set I played really good tennis. I had some tough times, but this score shows I was dominating a little bit," Nishikori, who next plays Bulgaria's Grigor Dimitrov, told reporters.
"I'm still not 100 percent yet, but feeling pretty strong. We'll have to see after a couple of more matches, but right now I feel good."
A confident Gael Monfils extended his recent run of form with a 7-6(5) 2-6 6-4 minor upset of Belgian seventh seed David Goffin to book his spot in the quarter-finals.
The 10th-seeded Frenchman, who arrived in Toronto fresh off earning his first tournament win in two-and-a-half years, will play Raonic in the quarters, after the local favourite dusted off American qualifier Jared Donaldson 6-2 6-3.
"I'm going for the shots," Wimbledon runner-up Raonic said.
(Reporting by Frank Pingue; Editing by Andrew Both and John O'Brien)
