Two-time Wimbledon champion Andy Murray joined Emma Raducanu through the exit door after a four-set defeat by John Isner.
Big-serving American Isner secured a first career victory over the Scot at the ninth attempt, firing down 36 aces in a 6-4 7-6 (7-4) 6-7 (3-7) 6-4 win.
The Scot managed to win only 15 points against the relentless Isner first serve.
But there was so much more to the 20th seed's victory, with a host of neat drop shots and deft touches at the net leaving Centre Court stunned.
- Wimbledon: Women's Draw I Men's Draw I Order of Play I News in brief
- Join our live daily blog for regular updates
- Kyrgios admits spitting in direction of abusive fan | Slams 'old' line judge
- Get Sky Sports | Download the Sky Sports App
Murray still believes he can still produce his best tennis at the Slams, indicating in his press conference that he has no intention of stepping away from the game.
"I think most of the players on the tour would tell you that a match like that was won or lost based on a few points here and there. I didn't play well enough on those points tonight," said the 35-year-old.
"Like I said, I certainly didn't serve well enough at the beginning of the match, which I think is understandable. Look, he's a difficult opponent to play against. Like you say, I obviously played well against him in the past.
"Tonight's match, I don't see why it should change that, change that view really."
He later added: "Physically I feel good, then we'll try to keep playing.
"But it's extremely difficult with the problems I've had with my body in the last few years to make long-term predictions about how I'm going to be even in a few weeks' time, never mind in a year's time.
"If physically I'm in a good place, yeah, I will continue to play. But it's not easy to keep my body in optimal condition to compete at the highest level."
Murray's serve needed to be firing as well, but too often in the early stages he gave Isner a look at his second attempt, and it was a searing return which was too hot for the home favourite as he was broken in the third game.
It was only the second time Isner had broken the Murray serve in 25 sets of tennis over the last 12 years.
The second set whizzed by with neither player laying a glove on the other, but Isner drew first blood in the tie-break and when Murray got a solitary chance to retrieve the damage he dumped a simple pass into the net.
On set point, Murray did well to get a racket on the 136mph rocket, but the return floated wide and Isner had a 2-0 lead.
In the inevitable third-set tie-break errors from Isner crept in for the first time, a long forehand and a volley into the net giving Murray the initiative and the fired-up former champion jumped wildly in delight as he halved the deficit.
However, he was crestfallen soon after when another simple backhand pass crashed into the tape to hand Isner break point, which he took with a return that Murray could only net.
With Isner leading 4-2 and the light fading the roof was closed. 10 minutes after the resumption, so was the latest chapter in Murray's Wimbledon odyssey.
"I am most definitely not a better tennis player than Andy Murray, I might have just been a little better than him today," said Isner after the Scot had left the cheering court, waving as he went.
"It was an incredible honour to play him on this court in front of this crowd. At the age I'm at now, I need to relish these moments. This was one of the biggest wins of my career," he added.
"To play as well as I did against one of our greatest players ever was a huge accomplishment for me. He's a massive inspiration to each one of us in the locker room and we are so lucky to still have him around."
Cameron Norrie survived a big scare to ensure the British No 1 made it through to the third round after a 6-4 3-6 5-7 6-0 6-2 victory over Juame Munar.
The friendly nature between the former doubles partners may have ended had the Spanish right-hander maintained his level throughout an exciting back-and-forth battle on Court One.
Norrie made sure he prevented any further misery for home players on the third day of the Championships by coming back to triumph in five sets not long after Emma Raducanu had exited in round two to Carolina Garcia.
Ryan Peniston's impressive summer on British soil is over after he lost in straight sets to American Steve Johnson.
Peniston reached the quarter-finals at Nottingham, Queen's and Eastbourne but he lost 6-3 6-2 6-4 in the second round on his maiden Grand Slam appearance.
The 26-year-old from Southend was unable to produce the level that had seen him shine in recent weeks, with the big-serving American seeing it out with ease.
Venus to partner Jamie Murray in mixed doubles; Edmund returns
The crowd-pleasing partnership of Jamie Murray and Venus Williams headlines the mixed doubles draw at Wimbledon, while Kyle Edmund makes his long-awaited return to tennis.
After Andy Murray and Serena Williams' attention-grabbing run to the third round in 2019, this time it is the turn of their siblings.
Venus, who is now 42, had said she would not be playing at Wimbledon this year but decided to follow her sister across the Atlantic and will bid to claim a first mixed doubles title at a Grand Slam for 24 years.
Jamie Murray has won five slam mixed doubles titles, including two at Wimbledon - in 2007 with Jelena Jankovic and Martina Hingis in 2017.
They will take on New Zealand's Michael Venus and Pole Alicja Rosolska in round one while former British No 1 Edmund partners fellow home player Olivia Nicholls against American duo Coco Gauff and Jack Sock.
- Serena's Wimbledon dreams ended in late-night epic I 'Who knows where I'll pop up'
- Everything you need to know about Wimbledon
- A year in the life of Emma Raducanu
Edmund has been sidelined since October 2020 with a knee problem that has proved stubbornly difficult to fix.
But this is an indication he is at last nearing full fitness ahead of a hopeful return to singles action later this summer.
Britain's Neal Skupski and American Desirae Krawczyk, the defending champions, are the second seeds behind Ena Shibahara of Japan and Dutchman Jean-Julien Rojer.
Join us for coverage from the All England Club with our daily live blog through skysports.com/tennis our Twitter account @skysportstennis & Sky Sports - on the go! Available to download now on - iPhone & iPad and Android