US second seed Gauff arrived at the All England Club with high hopes after winning the French Open last month but was beaten 7-6 (7/3), 6-1 by Ukranian world number 42 Dayana Yastremska.

Other high-profile casualties on day two of the grass-court Grand Slam were women's third seed Jessica Pegula and fifth seed Zheng Qinwen.

Instead of building on her success on the Paris clay, 21-year-old Gauff suffered her earliest Grand Slam exit since another first-round loss at Wimbledon in 2023.

The two-time Grand Slam champion said she would learn from her experience, suggesting she would like more grass-court tennis in the build-up to Wimbledon in future.

"I feel like mentally I was a little bit overwhelmed with everything that came afterwards (following the French Open triumph), so I didn't feel like I had enough time to celebrate and also get back into it," said Gauff.

"But it's the first time in this experience of, like, coming off a win and having to play Wimbledon. I definitely learned a lot of what I would and would not do again."

Earlier, US Open runner-up Pegula suffered a shock defeat against Italy's Elisabetta Cocciaretto, losing 6-2, 6-3 and was followed out of the tournament by Olympic champion Zheng, who went down 7-5, 4-6, 6-1 against unheralded Katerina Siniakova.

Men's third seed Alexander Zverev also bowed out, beaten in five sets by French world number 72 Arthur Rinderknech, giving a bleak assessment of his state of mind after the match.

The German, who reached the Australian Open final earlier this year, suffered his earliest Grand Slam exit since 2019 after a marathon match that started on Monday evening.

Afterwards he made surprisingly frank comments, saying he was considering therapy to talk through his mental health issues.

"It's funny, I feel very alone out there at times," he said. "I struggle mentally. I've been saying that since after the Australian Open."

- 'Miracle pills' -

Seven-time champion Djokovic was kept waiting until the evening to make his return to Centre Court as he targets a record 25th Grand Slam, which would take him clear of his tie with long-retired Margaret Court.

The veteran Serb struggled with feelings of discomfort and dropped a set but recovered to beat French world number 41 Alexandre Muller 6-1, 6-7 (7/9), 6-2, 6-2 in the final match on Centre Court.

Afterwards he admitted he had found it tough.

"I went from feeling my absolute best for a set and a half to my absolute worst for about 45 minutes," he said.

"Whether it was a stomach bug, I don't know what it is.

"I struggled with that but the energy came back after some doctors' miracle pills and I managed to finish the match on a good note."

Earlier, Krejcikova, who came to Wimbledon with just six matches under her belt this year, overcame a sluggish start to beat Philippines star Alexandra Eala 3-6, 6-2, 6-1.

Krejcikova has endured a difficult time since defeating Italy's Jasmine Paolini in the final last year.

The 29-year-old was out of action this season until May after suffering a back injury and pulled out of last week's Eastbourne Open before the quarter-finals with a thigh problem.

"I was in a lot of pain in my back and I didn't really know how my career was going to go," she said. "I'm super happy and super excited that I can be here and that I can play on such a great court."

Men's world number one Jannik Sinner brushed aside fellow Italian Luca Nardi 6-4, 6-3, 6-0 with a minimum of fuss.

Five-time Grand Slam winner Iga Swiatek swatted aside Russia's Polina Kudermetova 7-5, 6-1.

Two-time Wimbledon champion Petra Kvitova lost in straight sets in an emotional farewell appearance against US 10th seed Emma Navarro.

There were also wins for men's fourth seed Jack Draper and fifth seed Taylor Fritz.