The Serbian six-time champion, seeking to win the title for the fourth straight time, was made to work for his somewhat laborious 6-3 3-6 6-3 6-4 victory over Korean Soonwoo Kwon under the centre court roof on Monday.
The No.1 seed was out of sorts at times yet still notched up an extraordinary new milestone as he became the first player, man or woman, to record at least 80 singles victories at all four grand slams.
After being warmly applauded at the scene of his final victory over Matteo Berrettini in last year's event, Djokovic told the returning sell-out crowd in the sport's most famous arena: "This court is truly special for me ... it's an honour and pleasure to come back."
For Djokovic, down to No.3 in the rankings for the first time in four years, it was a tough two-hour, 27-minute opener, thanks to the enterprise of the Korean world No.81, who battled back from a set down with his variety of drop shots and aggressive groundstrokes.
He had the Serb on his toes too when he earned a break point to make life difficult for Djokovic in the third too until the champion began to find his familiar rhythm.
"I didn't have any lead up tournaments so you're always likely to feel less comfortable at the beginning, especially when you're playing someone as talented as Kwon," said the 20-time grand slam winner.
"Credit to Kwon for playing some really high quality tennis, he deserves some applause definitely."
Djokovic, who set up a second-round meeting with Australian Thanasi Kokkinakis, a straight-sets victor over Poland's Kamil Majchrzak, has now won his last 22 matches at Wimbledon stretching back five years to when he retired against Tomas Berdych in the 2017 quarters.
The first big shock of the tournament had seventh Hubert Hurkacz, semi-finalist last year and a recent winner in the Halle grass-court event, knocked out by Alejandro Davidovich Fokina 7-6 (7-4) 6-4 5-7 2-6 7-6 (10-8).
Victory for the talented young Spaniard, though, only came after he'd earlier almost thrown away victory in the most cavalier fashion, playing a baseline tweener when holding three match points at 5-3 in the third set.
His blooper enabled Hurkacz to regroup and fight back to two sets all, before Davidovich Fokina was left mightily relieved to finally squeeze through the first-to-10-point tiebreak decider.
French Open finalist Casper Ruud, the No.3 seed despite previously having lost four of his career tally of just six grass-court matches, battled through his opener for a maiden Wimbledon win, beating Spanish grinder Albert Ramos-Vinolas 7-6 (7-1) 7-6 (11-9) 6-2.
Ruud, who'd once joked that grass was for golfers, was helped by 14 aces as he finally broke down the baseline resistance of 34-year-old Ramos-Vinolas.