The big-serving American, ranked at number 41 in the world, had led by two sets to love overnight in a rain-affected contest and was able to see out a 7-6, 6-1, 3-6, 7-6 triumph amid rapturous applause on Court One at the All England Club.

The defeat ends the Serbian’s dream of a calendar Grand Slam as he arrived in London having already clinched the Australian Open and French Open crowns.

The loss was also Djokovic’s first at a major since he was beaten by Switzerland’s Stanislas Wawrinka in the final at Roland Garros last year and ended a 30-match Grand Slam winning streak.

It also opens up the men's draw and leaves Britain's Andy Murray as the favourite for the title.

The world number two remained coy when news of Djokovic's defeat filtered through to Centre Court as he swiftly dispatched Australia's John Millman 6-3, 7-5, 6-2.

“It's incredible, especially to do it here at Wimbledon,” Querrey told the BBC.

“I'm so ecstatic, so happy.

“I think today I played the break points well.

“Every time he had a break point I was able to come up with a big serve.

“He came out and got the first four games, fortunately for me we had another rain delay and I got to regroup.”

Djokovic, the current world number one, had seemingly hauled himself back into the contest as he raced into a 4-0 lead in the third set when play resumed this afternoon.

Querrey, who stands at an imposing six foot six inches, remained calm and moved into a 6-5 lead in the fourth before the rain came down just as Djokovic prepared to serve to stay in the contest.

The Serbian duly held to send the finely-poised fourth set into a tie-break, which the American managed to win to seal a remarkable victory and condemn Djokovic to his earliest Grand Slam exit since the 2009 French Open.

Japanese fifth seed Kei Nishikori had no such troubles as he progressed to round four with a comfortable 7-5, 6-3, 7-5 win over Russia’s Andrey Kuznetsov.

In the women’s draw, two-time winner Petra Kvitova of the Czech Republic lost 7-5 7-6 to Russia's Ekaterina Makarova, while Canadian Eugenie Bouchard is also out following a 6-4 6-3 defeat to 19th-seeded Slovakian Dominika Cibulkova.

Romania’s Simona Halep, seeded fifth, overcame Kiki Bertens of The Netherlands 6-4, 6-3 as the rain continued to wreak havoc on proceedings.

The poor weather throughout the opening week of the tournament has forced organisers to schedule play for tomorrow, traditionally the competition's rest day, for the first time in 12 years.