Like Djokovic, last year’s runner-up Taylor Fritz also dropped the first set but came through 4-6 7-6 (7-3) 6-2 6-4 against South Africa’s Lloyd Harris.
Fourth seed Fritz, the highest-ranked American in the men’s singles draw, will now face Jerome Kym after the Swiss qualifier upset 30th seed Brandon Nakashima of the USA in a marathon four hours and 20 minutes.
Twelfth seed Casper Ruud became the second-highest men’s seed to fall so far, losing in five sets to Belgium’s Raphael Collignon.
World number 107 Collignon, playing in his first Grand Slam main draw, came back to win 6-4 3-6 3-6 6-4 7-5 against the 2022 US Open runner-up.
It completes a miserable year of Grand Slam results for Norwegian Ruud, who also lost in the second round of the Australian and French Open, and missed Wimbledon with a knee injury.
Collignon now meets 20th seed Jiri Lehecka, who progressed with a 3-6 6-0 6-2 6-4 win over Argentina’s Tomas Martin Etcheverry.
Meanwhile, 21st seed Tomas Machac saw off rising Brazilian star Joao Fonseca in 7-6 (7-4) 6-2 6-3.
The 19-year-old Fonseca, backed by a boisterous fan base on the Grandstand court, had a set point in the opener but Machac held firm to prevail.
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