At the other half of the draw will be Rafael Nadal, the toughest rival a player can face and current No. 2; while last year's runner-up Juan Martin del Potro won't take part in the tournament due to an injury, reports Efe news.
Djokovic is the favourite to earn a fourth US Open following his success in 2011, 2015 and 2018.
Should he win, he will be the first player to clinch two titles back to back since Swiss great Roger Federer in 2008 when he earned his fifth consecutive title.
The Serb will aim at getting past his defeat in the Cincinnati Masters semifinal to Russia's Daniil Medvedev, who proved to be the most consistent as he won one of the three finals that he reached in August.
Djokovic, winner of the 2019 Australian Open and Wimbledon, will seek his 17th major title closing the gap with Nadal, the second most successful player in Grand Slams who won his 18th title at the 2019 French Open.
Federer tops the list of most successful player in Grand Slams with 20 crowns.
The 32-year-old will start his title defence run against Spaniard Roberto Carballes, 26, who will have a chance to face-off against the best in the world for the first time in his career.
In a potential quarterfinal, he would take on Medvedev, the fifth seed, having learnt his lesson after the Cincinnati defeat.
Nadal, meanwhile, arrives at Flashing Meadows seeded No. 2. The Spaniard will kick off his US Open run with John Millman of Australia, who stunned Federer in the 2018 edition of the fourth Grand Slam event of the season.
( With inputs from IANS )