Seven-time champion Djokovic, who could meet Sinner in the semi-finals, began his latest pursuit of an outright-record 25th major title by overcoming Frenchman Alexandre Muller 6-1 6-7 (7-9) 6-2 6-2 on Centre Court.
The Serb appeared to struggle early in the third set – later confirming that “something was off with the stomach” – but rediscovered his form following a medical timeout to win 10 of the final 12 games.
“I went from feeling my absolute best for a set and a half to my absolute worst for about 45 minutes. Whether it was a stomach bug, I don’t know what it is,” Djokovic said.
“I struggled with that but the energy came back and I managed to finish the match on a good note.”
Contesting his first Grand Slam match since losing one of the all-time great French Open finals to Carlos Alcaraz last month, world number one Sinner lost just seven games in a dominant a 6-4 6-3 6-0 win over fellow Italian Luca Nardi.
But Germany’s Zverev became the fourth top-10 ranked men’s player to exit the tournament across the first two days of action.
Defeats for third seed Zverev and Italy’s Lorenzo Musetti came on a day when French Open champion Coco Gauff became the third top-five seed to lose in the women’s draw.
Djokovic survives eventful opener
Novak Djokovic has never lost in the Wimbledon first round in 19 appearances
Djokovic stated before the tournament his belief that Wimbledon offers his best chance of disrupting the dominance of Carlos Alcaraz and Jannik Sinner to land his 25th Grand Slam title.
The 38-year-old appeared set to cruise through his opener as he won six consecutive games and lost only two points on serve in a scintillating 30-minute first-set display.
But the remainder of the match proved a much sterner test of the former world number one’s resolve.
Djokovic could not find a way past an improving Muller, despite creating 11 break points – including four set points – before he was taken to a tie-break.
He also led that 5-2, only for the battling Muller to produce a stunning recovery in which he won seven of the next nine points to level the match before the roof was closed.
There was concern for Djokovic early in the third set when the sixth seed called a medical timeout amid an obvious shift in his body language.
The assistance he received from the doctor, in the form of a tablet, appeared to have an immediate effect as he wrested back control of the contest, rediscovering his former level to take the third set by winning five successive games.
Muller, who also received a medical timeout to have treatment on his right calf, continued to delight the crowd with his resistance and forced a first couple of break points on Djokovic’s serve at the beginning of the fourth set.
But Djokovic, outstanding on serve throughout, held firm before making his break for the finish line – eventually serving out the match to love less than 30 minutes before the 23:00 BST play curfew.
He will face Britain’s Dan Evans in the second round, having now won 40 of his past 42 matches at Wimbledon – his only two defeats coming against Alcaraz in the past two finals.
Sinner makes impressive start
Jannik Sinner has held the top ranking for 12 months, despite serving a three-month doping suspension this year
