Britons Alfie Hewett and Gordon Reid's remarkable run of 10 consecutive Grand Slam wheelchair doubles titles was ended by Gustavo Fernandez and Shingo Kunieda in the Wimbledon final.
Japan's Kunieda and Argentine Fernandez defeated the top seeds 6-3 6-2.
Hewett and Reid, 15-time Grand Slam doubles champions, had not lost a major final since Wimbledon in 2019.
Earlier, Dutch top seed Diede de Groot beat Japan's Yui Kamiji to claim an eighth successive Grand Slam title.
De Groot, 25, won 6-4 6-2 to secure her 15th Grand Slam singles title and a fourth Wimbledon triumph.
Having become the first women's wheelchair player to complete a calendar Grand Slam last year, the straight-set victory also extended her remarkable winning streak to 56 matches.
Hewett and Reid's incredible run comes to an end
Four-time Wimbledon champions Hewett and Reid had won four of the past five doubles titles at SW19 since first teaming up at Wimbledon in 2016.
On a dramatic Friday at the All England Club, Hewett produced a stunning comeback against Fernandez to reach his first Wimbledon men's wheelchair singles final, before he and Reid prevailed in a tense final-set tie-break against Dutchman Tom Egberink and Belgium's Joachim Gerard.
The pair finished playing at 22:00 BST, with Hewett clocking a total of five hours 49 minutes on court in an exhausting day.
Reid's participation at Wimbledon had been in doubt after the Scot ruptured a tendon in his wrist during their successful French Open campaign.
"Congratulations to Shingo and Gustavo. They deserved to be the winners today. Under the circumstances, with what happened yesterday and the lack of time I've had on court recently, this was one ask too many," Reid said following Saturday's defeat.
Hewett said: "They've been desperate to beat us for some time now - the last time we lost in a Grand Slam was here in 2019 - but obviously yesterday was a massive day for us."
He added: "It was an incredible day that I will always remember and today it was challenging to get up and go again.
"We'll be back hopefully stronger than ever next year."
Hewett and Reid defeated Fernandez and Kunieda in the French Open final in June as they lifted their 10th consecutive major title.
Despite their late finish the previous night, it was the British pair who landed the first blow of their latest meeting in the Wimbledon final to take a 2-1 lead.
However, Fernandez and Kunieda responded impressively, breaking back immediately and striking again in the eighth game before serving out the first set.
The second seeds maintained their momentum at the start of the second set, breaking serve to love and consolidating that advantage with a love hold.
Hewett and Reid were unable to force their way back into the contest and saw their serve broken again as they fell 4-1 behind, before Fernandez and Kunieda sealed victory with a final break.
Hewett will contest his first Wimbledon men's wheelchair singles final against Japanese top seed Kunieda on Sunday at 11:00 BST.
"It feels amazing for us, together we have been struggling and working really hard to try to beat these guys," said Fernandez.
"They have given us a really big challenge so for us to win a doubles title together again after a while is amazing and we're really happy," he added.
"Yesterday for me personally was a really tough day so to come out again and get the victory is very important."
Kunieda said: "Gordon and Alfie are the best team in wheelchair history. It was a big challenge for us but finally we got there. I'm really happy."