Defending champion Novak Djokovic racked up his 90th win at the US Open on Wednesday by defeating Serb compatriot Laslo Djere who retired in the third set of their second round clash.

Djokovic, a four-time champion at the tournament and seeking a record 25th Grand Slam title, was leading 6-4, 6-4, 2-0 when Djere called it quits.

The world 109, who pushed his countryman to five sets in New York last year, needed a medical time-out to treat an injury just before dropping the second set.

The 37-year-old Djokovic had himself required a visit from the trainer for what appeared to be a side strain after sealing the first set.

World number two Djokovic is now the only man to have won 90 matches at all four Grand Slams.

"It's not what we want to see when there's a retirement. Laslo had an injury which took him off the tour for some time and he's been struggling to come back," said Djokovic.

"He's such a good player in these conditions and the second set should have been his, he was 4-2 up. I don't know if my winning the second set probably put more burden on him."

Djokovic will next meet Australia's Alexei Popyrin who he defeated at the Australian Open and Wimbledon this year with both matches going to four sets.

Popyrin is on a rich vein of form having won the Montreal Masters on the eve of the US Open. (AFP)