The Serbian, who has won 24 majors, defeated Stefanos Tsitsipas in last year’s final then added the French and US Open titles to his collection.
But the 36-year-old will begin his defense under an injury cloud after a wrist problem hampered him at the United Cup, where he lost to Australian Alex De Minaur.
Greek seventh seed Tsitsipas has a tough task to repeat his 2023 feat with former top 10 Italian Matteo Berrettini his opening opponent and Djokovic a potential quarter-finalist.
Spanish world number two Carlos Alcaraz, the only man to beat Novak Djokovic at a Slam last year to win Wimbledon, gets his campaign underway against French veteran Richard Gasquet.
Like Djokovic, third seed Daniil Medvedev, a Melbourne finalist in 2021 and 2022, drew a qualifier in the first round.
The Russian could face 27th seed Felix Auger-Aliassime in the third round, with the Canadian facing a stern opening test against former world number three Dominic Thiem.
On the women’s side, Polish top seed Iga Swiatek will open her account with a blockbuster rematch of the 2020 Roland Garros final that she won against Sofia Kenin, who went into that match as the Australian Open champion.
There will be no let-up for whoever wins, with a second-round clash looming against either 2016 Australian Open winner Angelique Kerber or 2022 Melbourne Park finalist Danielle Collins.
Two-time champion Naomi Osaka also faces a daunting task after being pitted against French 16th seed Caroline Garcia in her first major since having a baby.
Another bumper showdown will see third seed Elena Rybakina, last year’s runner-up, take on former world number one Karolina Pliskova.
Second seed and defending champion Aryna Sabalenka should have an easier time, she was drawn against a qualifier.