Alaphilippe (Quick-Step Floors) won the stage on the final descent on the 218 kilometre route from Carcassonne to Bagnères-de-Luchon with Gorka Izagirre (Bahrain Merida) second and Adam Yates third (Mitchelton-Scott).
Yates led the race across the top of Col du Portillon after attacking the breakaway but with Alaphilippe in hot pursuit. The pressure of the descent forced a crash for the British star and the eventual stage winner rode past the fallen front-runner with a handful of kilometres left to ride.
He rolled through the finish-line to take his second victory of the 2018 Tour, celebrating in his polka dot jersey that he wears as the leader of the King of the Mountains classification.
"Today it was a really crazy day," said Alaphillipe. "I had pain in the legs, but I don't think I was the only one suffering. I knew the finale, with the climb and the downhill, but I still can't believe that I won again.
"Taking two victories, one in the Alps and another one in the Pyrenees, is mind-blowing, I will never forget this day."
Alaphillipe reflected on the dramatic nature of his victory, sweeping past a fallen Adam Yates on the descent into the finish.
"The last 20 kilometers were very intense," said Alaphilippe, "with a lot of attacks and cat-and-mouse game in the escape. When I got word that Yates opened a half a minute gap, I decided to attack and managed to pull him back to ten seconds by the time he crashed.
"It's never nice when this happens to someone, and I waited for him, but then I saw he was hesitating a bit, so I continued my race."
General classification fireworks were held for another day as the favourites kept their powder dry for a short but potentially explosive Stage 17.
Geraint Thomas leads Team Sky team-mate Chris Froome with Tom Dumoulin (Sunweb) and Primoz Roglic (LottoNL-Jumbo) among the remaining contenders.
It was the second stage win for Alaphilippe who prevailed on the 10th stage in Le Grand Bornand. He also leads the mountains classification by a good margin agter his main competitor, Warren Barguil dropped off the pace in the breakaway.
The peloton and the audience held its collective breath when Philippe Gilbert (Quick-Step Floors), who had ridden away solo from the bottom of the ascent to Portet d’Aspet to a 55 second lead over a chasing group led by team-mate Alaphilippe, crashed in a ravine before emerging from the bush to remount his bike.
The stage was briefly interrupted with 187km left to race by a farmers’ protest, police using tear gas to disperse the demonstrators with some riders being affected by the gas.
They were 17 riders together at the bottom of the Col du Portillon, the last climb of the day, with the peloton cruising 11 minutes behind. Five kilometres before the summit, Robert Gesink (LottoNL-Jumbo), Dominico Pozzovivo (Bahrain-Merida) and Bauke Mollema (Trek-Segafredo) took up the pace.
With three kilometres of climbing left, Yates rode away solo and crested the Col du Portillon 15sec before Alaphilippe. But he crashed in the downhill with seven kilometres to go and the polka dot jersey holder shot past to seal a solo victory in Bagnères-de-Luchon.
The yellow jersey group holding the favourites crossed the line with a deficit of 8min 52sec.
Peter Sagan (BORA-hansgrohe) virtually secured a record-equaling sixth green jersey for the points classification, which he will officially wrap up if he reaches Paris. He leads Alexander Kristoff (UAE Team Emirates) by an unassailable 282 points with 270 still up for grabs.