Marketa Vondrousova became the first defending women's Wimbledon champion to lose in the first round for 30 years on Tuesday as Novak Djokovic and Iga Swiatek cruised through.
Off the court, two-time champion Andy Murray pulled out of the singles at his farewell All England Club appearance because he has not recovered sufficiently from recent back surgery.
It was a painful day for Czech sixth seed Vondrousova, whose time in the Wimbledon spotlight was cut cruelly short in a chastening 6-4, 6-2 defeat to Spain's unheralded Jessica Bouzas Maneiro.
Vondrousova is only the second defending champion to lose in the first round at the All England Club in the Open Era.
The only other time it happened was 30 years ago, when Lori McNeil defeated three-time defending champion Steffi Graf.
World number 83 Bouzas Maneiro, playing in only the third Grand Slam main draw of her career, broke five times in the match under the roof on Centre Court, sealing victory in 66 minutes.
Vondrousova, who said she was wary in her first match since she hurt her hip at last month's Berlin grass-court tournament, struggled with her serve and racked up 28 unforced errors.
"Practice was fine and everything," said the 25-year-old Czech. "Today I was a bit scared because of my leg too. But I don't think that was the reason. I felt nervous from the start."
She added: "It's tough to go out defending the title."
There were no such problems for world number one Swiatek, who beat former Australian Open champion Sofia Kenin 6-3, 6-4.
The Polish top seed, who was playing her first match since winning a fourth French Open title last month, said she was happy with her performance after switching from clay to grass.
"I feel like I'm making progress every year, and every year is a little bit faster for me, the process of adapting to the surface," said the 23-year-old, a quarter-finalist last year.
Elena Rybakina, the 2022 champion, cantered past Romania's Elena-Gabriela Ruse 6-3, 6-1 while fifth seed Jessica Pegula lost just two games against US compatriot Ashlyn Krueger.
Dominant Djokovic
Djokovic, 37, had a knee operation after pulling out before his French Open quarter-final – sparking fears he would not be fit in time for Wimbledon, where he is chasing a record-equalling eighth men's title.
But although he wore a support on his right knee he showed no sign of discomfort in dispatching Czech qualifier Vit Kopriva 6-1, 6-2, 6-2.
The Serbian world number two, who was beaten by Carlos Alcaraz in last year's final, did not face a single break point during his cruise.
He knows time is not on his side as he bids to equal Roger Federer's Wimbledon title haul and also become the first player – man or woman – to win 25 Grand Slam singles titles.
"I tried to really focus on the game and not think about the knee too much," said Djokovic.
"Everything that I could do, I have done over the last three weeks along with my team to be able to play here for you today.
"I think if it was for any other tournament I probably would not have risked it, would not have rushed as much but I just love Wimbledon, love coming back here."
A fuming Andrey Rublev, a quarter-finalist last year, exited in four sets against Argentina's Francisco Comesana, playing his first Grand Slam match.
The Russian sixth seed repeatedly smashed his racquet against his knee in the third set as his frustration mounted but he failed to turn things around and lost 6-4, 5-7, 6-2, 7-6 (7/5).
Fourth seed and French Open runner-up Alexander Zverev progressed in straight sets.
Britain's Murray, 37, is hoping to end his stellar career at the upcoming Paris Olympics but desperately wanted to make a final singles appearance at Wimbledon, where he was champion in 2013 and 2016.
The Scot, who has been ravaged by injuries in recent years, will still play doubles with his brother Jamie, with whom he practised on Tuesday afternoon.
"I'm disappointed, I wanted to play in the tournament," he said. "I wanted to have a chance to go out there and walk out on my own on the Centre Court again and give it another go.
"But I also was only going to do that if I felt like I could be competitive and I didn't feel like that today. I'm sorry for everyone that came and wanted to support and watch again.”
Wimbledon results - Tuesday
Men’s first round
Ben Shelton (USA x14) bt Mattia Bellucci (ITA) 4-6, 6-3, 3-6, 6-3, 6-4
Francisco Comesana (ARG) bt Andrey Rublev (RUS x6) 6-4, 5-7, 6-2, 7-6 (7/5)
Adam Walton (AUS) bt Federico Coria (ARG) 6-3, 6-3, 7-5
Luciano Darderi (ITA) bt Jan Choinski (GBR) 7-5, 4-6, 2-6, 7-5, 6-2
Lorenzo Musetti (ITA x25) bt Constant Lestienne (FRA) 4-6, 7-6 (7/4), 6-2, 6-2
Giovanni Mpetshi Perricard (FRA) bt Sebastian Korda (USA x20) 7-6 (7/5), 6-7 (4/7), 7-6 (8/6), 6-7 (4/7), 6-3
Yoshihito Nishioka (JPN) bt Nuno Borges (POR) 6-2, 7-6 (8/6), 2-6, 6-3
Stefanos Tsitsipas (GRE x11) bt Taro Daniel (JPN) 7-6 (7/5), 6-4, 7-5
Taylor Fritz (USA x13) bt Christopher O'Connell (AUS) 6-1, 6-2, 6-4
Flavio Cobolli (ITA) bt Rinky Hijikata (AUS) 7-5, 4-6, 6-4, 6-4
Jack Draper (GBR x28) bt Elias Ymer (SWE) 3-6, 6-3, 6-3, 4-6, 6-3
Cameron Norrie (GBR) bt Facundo Díaz (ARG) 7-5, 7-5, 6-3
Marcos Giron (USA) bt Henry Searle (GBR) 3-6, 6-3, 6-4, 6-4
Alexander Zverev (GER x4) bt Roberto Carballes Baena (ESP) 6-2, 6-4, 6-2
Hubert Hurkacz (POL x7) bt Radu Albot (MDA) 5-7, 6-4, 6-3, 6-4
Arthur Fils (FRA) bt Dominic Stricker (SUI) 6-3, 6-2, 3-6, 6-4
Jaume Munar (ESP) bt Billy Harris (GBR) 6-4, 6-4, 3-6, 6-3
Alex De Minaur (AUS x9) bt James Duckworth (AUS) 7-6 (7/1), 7-6 (7/3), 7-6 (7/4)
Holger Rune (DEN x15) bt Kwon Soon-woo (KOR) 6-1, 6-4, 6-4
Thiago Seyboth Wild (BRA) bt Paul Jubb (GBR) 1-6, 3-6, 7-6 (8/6), 6-4, 7-5
Tomas Etcheverry (ARG x30) bt Luca Nardi (ITA) 6-1, 6-4, 6-2
Alexei Popyrin (AUS) bt Thiago Monteiro (BRA) 6-4, 6-7 (8/10), 6-3, 6-4
Jacob Fearnley (GBR) bt Alejandro Moro Canas (ESP) 7-5, 6-4, 7-6 (14/12)
Novak Djokovic (SRB x2) bt Vít Kopriva (CZE) 6-1, 6-2, 6-2
Women’s first round
Iga Swiatek (POL x1) bt Sofia Kenin (USA) 6-3, 6-4
Petra Martic (CRO) bt Francesca Jones (GBR) 3-6, 6-1, 6-2
Yulia Putintseva (KAZ) bt Angelique Kerber (GER) 7-5, 6-3
Katerina Siniakova (CZE x27) bt Marina Stakusic (CAN) 6-4, 6-2
Caroline Garcia (FRA x23) bt Anna Blinkova (RUS) 6-4, 7-5
Bernarda Pera (USA) bt Anastasia Potapova (RUS) 6-7 (4/7), 6-4, 7-6 (10/6)
Daria Snigur (UKR) bt Océane Dodin (FRA) 6-4, 6-0
Jelena Ostapenko (LAT x13) bt Ajla Tomljanovic (AUS) 6-1, 6-2
Dalma Galfi (HUN) bt Mayar Sherif (EGY) 6-1, 6-2
Cristina Bucsa (ESP) bt Ana Bogdan (ROM) 6-4, 4-6, 7-6 (10/5)
Jessica Bouzas Maneiro (ESP) bt Marketa Vondrousova (CZE x6) 6-4, 6-2
Elena Rybakina (KAZ x4) bt Elena-Gabriela Ruse (ROM) 6-3, 6-1
Laura Siegemund (GER) bt Kateryna Baindl (UKR) 6-4, 6-1
Caroline Wozniacki (DEN) bt Alycia Parks (USA) 6-2, 6-0
Leylah Fernandez (CAN x30) bt Lucia Bronzetti (ITA) 6-4, 6-3
Anna Kalinskaya (RUS x17) bt Panna Udvardy (HUN) 6-3, 6-2
Marie Bouzkova (CZE) bt Julia Riera (ARG) 6-2, 6-1
Elina Avanesyan (RUS) bt Anhelina Kalinina (UKR) 6-2, 6-3
Liudmila Samsonova (RUS x15) bt Rebeka Masarova (ESP) 6-3, 4-6, 6-2
Ons Jabeur (TUN x10) bt Moyuka Uchijima (JPN) 6-3, 6-1
Robin Montgomery (USA) bt Olivia Gadecki (AUS) 6-4, 6-4
Katie Boulter (GBR x32) bt Tatjana Maria (GER) 7-6 (8/6), 7-5
Harriet Dart (GBR) bt Bai Zhuoxuan (CHN) 6-4, 6-0
Wang Xinyu (CHN) bt Viktoriya Tomova (BUL) 7-6 (7/4), 3-6, 6-0
Jessica Pegula (USA x5) bt Ashlyn Krueger (USA) 6-2, 6-0