The World No.1 had to fight back to defeat teenage star Carlos Alcaraz over five sets to make the second round.
Six-time champion and top seed Djokovic saw off South Korea's Kwon Soo-woo 6-3, 3-6, 6-3, 6-4.
But 20-time Grand Slam winner Djokovic was made to work after falling a break down in the opening two sets against his 81st-ranked opponent.
"Now we have got to 80 wins, let's get to 100," said Djokovic.
— Wimbledon (@Wimbledon) June 27, 2022
Djokovic, 35, is attempting to win a fourth successive Wimbledon title and join a select group.
In the Open era, only Bjorn Borg, Pete Sampras and Roger Federer have managed such a streak at the All England Club.
Next up for Djokovic is Thanasi Kokkanikis. "Novak is kind of a brick wall," said the Australian.
Alcaraz, a potential quarterfinal opponent for Djokovic, came back from two sets to one down to defeat Germany's Jan-Lennard Struff.
The 19-year-old fired 30 aces and 73 winners in a dazzling display of shot-making to win 4-6, 7-5, 4-6, 7-6 (7/3), 6-4.
"Last year, I played five sets in the first round here as well so this shows how much I like grass," joked Alcaraz.