Spanish star Alcaraz faces a potentially awkward route to the final where a possible showdown with world number one Jannik Sinner could be waiting at Flushing Meadows.
Alcaraz, who could supplant Sinner as world number one depending on results in New York over the next fortnight, will have to hit the ground running starting from Sunday.
The Spaniard faces big-serving American hope Reilly Opelka in the first round.
If the tournament follows seedings, the 2022 US Open champion will meet former world number one Djokovic in the semi-finals.
Djokovic, who is chasing a record 25th Grand Slam title, will begin his campaign against Learner Tien in the opening round.
Seventh seed Djokovic leads Alcaraz 5-3 in previous meetings, and defeated the Spaniard over four sets in the quarter-finals of the Australian Open earlier this year.
The 38-year-old Serbian icon’s form remains a mystery though heading into the final Grand Slam of the season. Djokovic has not played since his run to the semi-finals at Wimbledon last month.
Top seed and defending champion Sinner meanwhile will begin his campaign against Czech Vit Kopriva in the opening round.
The 24-year-old Italian, who retired during the first set of his Cincinnati Open final with Alcaraz earlier this week, could meet Britain’s Jack Draper in the quarter-finals.
In the women’s singles draw, world number one and defending Aryna Sabalenka will open her campaign against Switzerland’s Rebeka Masarova, the world number 109.
Second seed Iga Swiatek, the reigning Wimbledon champion and 2022 US Open winner, is in the other side of the draw and begins her bid for a seventh Grand Slam singles title against Colombia’s Emiliana Arango.
Swiatek’s path to the final could see her meet 2023 US Open champion Coco Gauff in the semi-finals. Gauff faces Australia’s Ajla Tomljanovic in the first round.
Elsewhere, Venus Williams faces a daunting task if she is to prolong what could be her farewell US Open appearance beyond the first round.
The 45-year-old US tennis icon was granted a wild card into the first round of the tournament, some 28 years after she reached her first US Open final as a 17-year-old in 1997.
Williams faces Czech 11th seed Karolina Muchova in the first round. (AFP)