Djokovic thumped 99th-ranked Yoshihito Nishioka of Japan 6-3, 6-1, 6-0 under the roof of Court Philippe Chatrier.
The top-seeded Serb, who turned 35 on Sunday, is playing his first major since losing the US Open final last September.
His attempt to defend his Australian Open title in January ended in chaos and controversy when he was deported from Melbourne for refusing to get vaccinated.
On Monday, in a chilly and damp Paris, Djokovic took his record in first round matches at Roland Garros to 18-0 with his win over the 27-year-old Nishioka after converting eight of 18 break points.
Djokovic will next meet either Slovakia's Alex Molcan or Federico Coria of Argentina.