The Serb second seed cruised to a 6-1, 6-2 thrashing of Spaniard Guillermo Garcia-Lopez and took less than an hour to extend his overall streak to 31, stretching back to the two Davis Cup final singles he won in December.
The record for a winning start to a season remains 42 matches, set by John McEnroe in 1984, with Bjorn Borg, who had 33 straight wins in 1980, in second spot.
Top-seeded holder Rafael Nadal went through to the last eight without lifting a racquet as opponent Juan Martin Del Potro retired before their third round match with hip pain.
Unseeded Del Potro, the 2009 US Open champion, who is making a recovery this season after missing more than eight months of play in 2010 after wrist surgery, had been bothered by the problem since reaching the Estoril semi-finals at the weekend.
Third seed Roger Federer got past Belgian Xavier Malisse 6-4, 6-3 after a late-night struggle on Wednesday against Feliciano Lopez which went three hours."It was a quick turnaround," said the two-time champion. "Mentally it was tough, I had to be ready to play a different kind of match (from the night before).
"I didn't have high expectations, I just wanted to play a good match. I was able to do that."
In the women's event, world number one Caroline Wozniacki lost to Germany's Julia Goerges for the second time in little more than a week while French Open champion Francesca Schiavone and Roland Garros runner-up Samantha Stosur also went out.
Goerges, who saw off Wozniacki in the Stuttgart final last week, enjoyed a 6-4, 1-6, 6-3 win and next plays Russian Anastasia Pavlyuchenkova, who upset Stosur 7-6 (7/4), 6-3.
"I'm quite proud of the last three weeks, I was able to play more aggressively today. I didn't give her any rhythm," said Goerges, the world number 27.
"I've been working hard on my fitness over the last 18 months and I think it's starting to show results."
America's Bethanie Mattek-Sands defeated third seed Schiavone 7-6 (7/5), 6-3 but there were no problems for fourth seed Victoria Azarenka who overcame Spain's Arantxa Parra Santonja 6-0, 6-3.
Sixth seed Li Na of China, the Australian Open finalist, continued her progress, moving into the last eight thanks to a 2-6, 6-2, 6-1 win over Italian Roberta Vinci, who won in Barcelona last weekend.
Results on the sixth day of the ATP/WTA Madrid Masters (x denotes seeding):
Men
Third Round
Rafael Nadal (ESP x1) bt Juan Del Potro (ARG) walkover (hip injury)
Novak Djokovic (SRB x2) bt Guillermo Garcia-Lopez (ESP) 6-1, 6-2
Roger Federer (SUI x3) bt Xavier Malisse (BEL) 6-4, 6-3
Women
Third Round
Julia Goerges (GER) bt Caroline Wozniacki (DEN x1) 6-4, 1-6, 6-3
Li Na (CHN x6) bt Roberta Vinci (ITA) 2-6, 6-2, 6-1
Victoria Azarenka (BLR x4) bt Arantxa Parra Santonja (ESP) 6-0, 6-3
Anastasia Pavlyuchenkova (RUS) bt Samantha Stosur (AUS x5) 7-6 (7/4), 6-3