Fifth seed Stan Wawrinka was knocked out by Daniil Medvedev in the biggest shock on day one of Wimbledon 2017.
The 32-year-old, a three-time Grand Slam champion, needed ice on a knee injury between points as he fell to a 6-4 3-6 6-4 6-1 loss on Centre Court.
Earlier, Rafael Nadal began his bid for a third Wimbledon title with a comfortable win over John Millman.
But world number 20 Nick Kyrgios failed to reach round two, retiring from his opening match because of a hip injury.
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Medvedev's victory over world number three Wawrinka came just hours after the 21-year-old moved into the world's top 50 for the first time.
It was his first Grand Slam victory on his Wimbledon debut, and he celebrated by dropping to the court in front of the net and kissing the ground.
"At 5-1, I started thinking about what to do after the match and I kissed the grass because it was my first Grand Slam win, even though people do it when they win Wimbledon," he said.
Medvedev lost in the first round at the Australian Open and Roland Garros earlier this year, but arrived at the All England Club feeling confident after an excellent start to his grass-court season.
The Russian reached the semi-finals at Eastbourne, losing to Novak Djokovic, and also made the last eight at Queen's and s'Hertogenbosch.
"I'm really happy," he said. "Wimbledon is my favourite Grand Slam. It was in my juniors and still is.
"One year ago I was 250th in the rankings and if someone said I would not only play on Centre but win I would say: 'You are joking!'
"I have had a great grass-court season and knew Stan had some problems. I knew I had a chance if I played good, and I played amazing."
Wimbledon continues to elude Wawrinka
Wawrinka, having already won the Australian, French and US Opens, was attempting to become only the sixth man to complete the career Grand Slam in the Open Era.
But the Swiss only played once on grass before Wimbledon, losing at Queen's to eventual champion Feliciano Lopez.
"I wasn't feeling the way I wanted to feel but I played against a great player," said Wawrinka, who has never gone past the quarter-finals in SW19.
"I had problems with the knee since Queen's. It is not something new but something I had in the past. Apparently grass is not the best surface for my knee and I need to figure out what I'm going to do and come back when I have no pain.
"I thought two weeks between Queen's and now would be enough but it wasn't. I'll talk to my team and doctor and take the time I need."
Analysis - 'Horrible draw for Wawrinka'
BBC tennis correspondent Russell Fuller
Medvedev's impressive English summer continued, inspired by his Centre Court surroundings on his Wimbledon debut. This always looked a horrible draw for Wawrinka, who has had some pain in his knee since switching from the clay to the grass.
A first-round defeat at Queen's Club left him short of practice and belief on what he describes as the "most challenging surface for my game".
Wawrinka had the opportunity this fortnight to become only the ninth man in history to have won all four Grand Slam titles, although given his record at Wimbledon, the odds were always very much against.
Nadal eases through on Wimbledon return
Spanish world number two Nadal beat Millman 6-1 6-3 6-2.
The win was the 850th of Nadal's career and came in his 50th match at Wimbledon.
He will next face American world number 43 Donald Young, who was 2-1 up in sets when opponent Denis Istomin retired.
Nadal missed last year's Wimbledon because of injury and was playing his first tournament match on grass in two years.
He is looking to secure a second Gram Slam title in 2017 after winning last month's French Open.
"I have been playing good tennis since the beginning of the season," said Nadal.
"The clay-court season has been special and emotional and here I have an opportunity to perform on grass."
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'It was not easy to pull out' - Kyrgios
Kyrgios was visibly struggling throughout his match with France's Pierre-Hugues Herbert and pulled out shortly after losing the second set, with the Frenchman leading 6-3 6-4.
The 20th seed withdrew from the Aegon Championships at Queen's Club last month after slipping during his first-round match with Donald Young.
"I did everything I could to help it. I did not have enough time," said the 22-year-old.
It is the first time Kyrgios has gone out in round one at Wimbledon.
Kyrgios said at the weekend he was only "about 65%" fit after aggravating the long-standing injury to his left hip at Queen's, but insisted it was not a career-threatening problem.
"Surgery? I don't know at the moment. I'm not a doctor," he said.
"I spoke to the doctor before the tournament and he leaned towards not playing. But it is my favourite tournament and it was not easy to pull out.
"I thought I could win. There are some opponents I probably still could have won against, but not Pierre. I'm not taking anything away from him."
Kyrgios pulled out of the Monte Carlo Masters and Italian Open earlier this season with the hip problem that resurfaced at Queen's.
Against Herbert, he tried to win as many points as possible with his serve, and was unable to move quickly enough to reach the Frenchman's passing shots.
Herbert will next meet compatriot Benoit Paire in round two after the 28-year-old beat Brazil's Rogerio Dutra Silva 6-4 3-6 7-6 (12-10) 6-4.
Elsewhere, Croatian seventh seed Marin Cilic had too much for world number 60 Philipp Kohlschreiber, beating the German 6-4 6-2 6-3.
Japanese ninth seed Kei Nishikori also progressed with a straight-set victory, defeating Marco Cecchinato of Italy 6-2 6-2 6-0.