Djokovic, a strong favourite to win on the men's side at Flushing Meadows this year in the absence of Roger Federer and Rafael Nadal was made to work for his third round place as he lost the first set on a tie-break to Britain's Kyle Edmund.

The Serbian battled back to win in four sets 6-7 6-3 6-4 6-2.

Elsewhere on the men's side two more top ten seeds recorded four set wins.

Alex Zverev, the fifth seed from Germany overcame American Brandon Nakishima 7-5 6-7 6-3 6-1 while David Goffin, the seventh seed from Belgium beat Lloyd Harris of South Africa 7-6 4-6 6-1 6-4.

On the women's side, top seed Karolina Pliskova suffered a shock straight sets loss to France's Caroline Garcia 6-1 7-6.

Garcia won the first set comfortably and went a break up early in the second set.

Pliskova offered some resistance breaking back to force a tie-break which Garcia took by seven points to two to seal the biggest upset of the tournament so far.

Elsewhere, two top ten seeds progressed with sixth seed Petra Kvitova beating Kateryna Kozlova of Ukraine 7-6 6-2 and eighth seed Petra Martic of Croatia overcoming Ukrainian Kateryna Bondarenko 6-3 6-4.

Pliskova was not the only women's seed to lose on day three, with others including 11th seed Elena Rybakina of Kazakhstan crashing out 7-5 6-1 to American Shelby Rogers, 12th seed Marketa Vondrousova of the Czech Republic losing convincingly 6-1 6-2 to Aliaksandra Sasnovich of Belarus and 13th seed Alison Riske of America losing heavily 6-0 6-2 to compatriot Ann Li.

Among the big names in action in the night session on day three are Japan's Naomi Osaka, the fourth seed, who plays Italian Camila Giorgi and men's fourth seed Stefanos Tsitsipas of Greece, who faces American Maxime Cressy.