Geraint Thomas saw his Tour de France hopes fade on the brutal slopes of the Tourmalet as he lost contact with the main favourites in the final kilometre before Thibaut Pinot took victory.
Scroll down for full stage-by-stage guide & odds
Julian Alaphilippe once again defied expectations to finish second in the yellow jersey while Welshman Thomas was distanced and finished 36 seconds after Pinot.
It was a dramatic finish to another stage which rewrote the general classification as contenders were dropped one-by-one on the Tourmalet, with Adam Yates and Dan Martin seeing their overall hopes effectively ended.
The new general classification shows Deceuninck-Quick Step's Alaphilippe has extended his lead over second-placed Thomas to two minutes and two seconds, while Steven Kruijswijk moves into third place ahead of Egan Bernal.
Alaphilippe had already defied predictions to pull out time on Thomas in Friday's time trial, but that it was the defending champion that cracked before him on the Tour's first hors categorie climb was an even bigger surprise.
Most observers still expect Alaphilippe's remarkable run in yellow to end sooner or later, but Thomas' rivals will have been hugely encouraged by his struggles here.
Kruijsiwjk is now only 12 seconds in arrears to Thomas after a big performance from his Jumbo-Visma team, while Emmanuel Buchman and Pinot are 70 seconds behind the Team Ineos man in fifth and sixth respectively.
Thomas hinted he may not be well, after the stage.
"Not the best day," he said.
"I just didn't feel quite on it from the start. I was quite weak. At the end I knew I just had to pace it. I didn't really attempt to follow when they kicked.
"I just thought I should ride my own pace rather than follow them and blow up on the steepest bit at the end. It's disappointing. I just tried to limit the damage."
Asked if he was unwell, Thomas said: "We will see the next few days. From the start I just didn't feel great. There's still a lot to come."
Tour de France: Stage-by-stage guide
July 21, Stage 15: Limoux to Foix Prat d'Albis (185.5km)
The second summit finish in a row comes on a more traditional Pyrenean stage, which rolls over several testing climbs, sapping the legs and the minds. However, there is no tradition to the finish with the Prat d'Albis making its Tour debut.
July 23, Stage 16: Nimes to Nimes (177km)
After the second rest day comes a pretty flat stage, though with constant changes of direction on a loop starting and finishing in Nimes, the sprinters' plans could be disrupted if the Mistral wind blows.
July 24, Stage 17: Pont du Gard to Gap (200km)
And so towards the Alps, though stage 17 features none of the big passes on a day of gradual climbing up to Gap. This is the stage in the race where breaks are often allowed to stay clear as the battle for yellow rages behind, but this day has been made to be utterly unpredictable. A punchy final climb of the Col de la Sentinelle could be a springboard, while it's not inconceivable some of the sprinters survive in the main group.
July 25, Stage 18: Embrue to Valloire (208km)
There may only be five HC climbs in the entire Tour, but two of them come in a single day as the riders tackle the Izoard and the Galibier before dropping down to the finish in Valloire. The stage winner should come from whichever group first crests the Galibier - appearing for the 60th time as the Tour's most regular Alpine venue - and this could be a decisive day overall.
July 26, Stage 19: Saint-Jean-de-Maurienne to Tignes (126.5km)
Stage 19 is a leg-sapping day designed to test the resolve of anyone planning a late move in the general classification. The Iseran - at 2,770m the high point of the Tour - comes in the middle of the stage and casts a long shadow before the shorter climb to Tignes offers an opportunity for attacks.
July 27, Stage 20: Albertville to Val Thorens (130km)
The last chance saloon for GC hopefuls does not look an inviting one. The final climb of the Tour is the 33.4km HC slog up to Val Thorens. If ever there was a Tour designed for a true climber, one with only a handful of time trial kilometres and four HC climbs in the last three days could be it.
July 28, Stage 21: Rambouillet to Paris Champs-Elysees (128km)
There are two big questions on the final day. Will the yellow jersey winner choose a few glasses of champagne or, as Geraint Thomas did last year, prefer a beer or two as they celebrate along the roads of the Parisian suburbs? And which sprinters will have survived the mountains in order to battle it out on the Champs-Elysees?