The Serb's bid for a record-extending 25th grand slam title looked like it might be under threat when Popyrin took a 4-3 lead with a blistering crosscourt forehand winner and sealed the opening set with a second-serve ace.
But normal service was soon resumed.
Appearing rejuvenated after the roof was closed, Djokovic went up 4-1 in the second set, when fans erupted on Centre Court as news trickled in that England had beaten Switzerland to make the Euro 2024 semi-finals.
The amused second seed simulated a penalty kick that Popyrin pretended to save, to the delight of fans.
Djokovic had little trouble in the second and third sets, but faced a bit more resistance in the fourth as Popyrin dug deep in search of his first win in the pair's third clash, saving three breakpoints to hold in the 11th game.
After ensuring a tiebreak, however, Djokovic switched on the after-burners to close out the win, finishing with a fiery serve that Popyrin could only send crashing back into the net.
After putting one shot into the net, Iga Świątek muttered to herself. After another point went awry, she placed her hand over her mouth. Generally, she looked as flustered as she ever does on a tennis court.
Once again, she went from unbeatable on the French Open's red clay to underwhelming on Wimbledon's green grass.
The number one-ranked Świątek's 21-match winning streak ended with a listless performance and a slew of mistakes on Saturday, adding up to a 3-6, 6-1, 6-2 loss to unseeded Yulia Putintseva in the third round at the All England Club.
"Going from this kind of tennis, where I felt like I'm playing the best tennis in my life, to another surface, where I kind of struggle a little bit more, it's not easy," said Świątek, who only once has made it as far as the quarterfinals at Wimbledon, exiting at that stage a year ago.
"All that stuff really combines to me not really having a good time in Wimbledon."
Never does. In 2022, for example, her 37-match unbeaten run was stopped with another third-round loss at the All England Club, that one to Alize Cornet.
Świątek, a 23-year-old from Poland, is a five-time grand slam champion, including four titles at Roland Garros — most recently last month — and one on the hard courts at the US Open.
She has talked looking forward to improving on grass, but she decided to withdraw last month from the only tune-up event that was originally on her schedule before Wimbledon.
"My tank of really pushing myself to the limits became, suddenly, empty," Świątek said. "I was kind of surprised."
As England football fans celebrated success of a different kind in Germany, a German player ended Britain's interest in the men's draw at Wimbledon.
Fourth seed Alexander Zverev survived an injury scare and an epic third-set tiebreak to beat Britain's Cameron Norrie and match his best Wimbledon run by reaching the fourth round for the third time.
The German produced a sensational display of serving to win 6-4 6-4 7-6(15) — finally ending Norrie's rugged resistance by converting his sixth match point under the Centre Court roof despite needing regular treatment for a knee injury he suffered in the second set.
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"I do feel like a cow on ice sometimes [on grass]," Zverev, who also beat Norrie in five sets at the Australian Open and leads their Tour head-to-head 6-0, said on court.
"It is what it is but I managed. I do feel restricted on some of the movements but I will check and see what it is but I'm pleased I was able to play the way that I did. If I'd dropped in my level I would have had no chance against Cam."
Zverev has bitter memories of injuries ending grand slam challenges, notably at the 2022 French Open when he had to be taken off court on a wheelchair during his semi-final against Rafa Nadal, having sustained serious ankle damage.
Speaking to reporters later he sounded confident that this knee injury was not too serious.
"If you're breaking a ligament or breaking something else, the meniscus or something like that, I don't think you can continue playing even the way I did, hopefully I'll be fine in two days' time," he said.
Andy Murray's Wimbledon career came to an anticlimactic end when Emma Raducanu, his mixed doubles partner, pulled out of that competition hours before their first-round match on Saturday because of an issue with her surgically repaired right wrist.
The 37-year-old Murray, a two-time singles champion at the All England Club, has said he will head into retirement after competing at Wimbledon and the Paris Olympics, which start later this month.
Mixed doubles was supposed to be the last event at the grass-court grand slam tournament for Murray, who withdrew from singles because of an operation to remove a cyst from his spine on June 22, and then exited in the first round of men's doubles alongside his older brother, Jamie.
"Unfortunately I woke up with some stiffness in my right wrist this morning, so therefore I have decided to make the very tough decision to withdraw from the mixed doubles tonight," Raducanu said.
"I'm disappointed as I was really looking forward to playing with Andy but got to take care."
American Ben Shelton claimed another five-set victory at Wimbledon this week, winning 6-7 (4), 6-2, 6-4, 4-6, 6-2 against Denis Shapovalov.
It was the 21-year-old American's third consecutive five-set win, the first player to do that at Wimbledon since Ernests Gulbis in 2018.
No man in the Open era (which dates to 1968) has ever won four matches in a row in five sets at any major tournament.
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There already have been 33 five-set matches through one week of play, the most ever at any slam in the Open era.
The most for an entire tournament in that span is 35.
Shapovalov chalked that up to there being talent spread around the tour and few grass-court experts.
Shelton said he loves that matches can go that long.
"There's a lot of things I appreciate five sets," Shelton said.
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