Froome crashed twice in Wednesday’s stage to add to another fall he’d had on Tuesday and it all proved too much for the 29-year-old Kenyan-born, British rider.
After his last spill he didn’t even try to climb back on his bike and headed for a Sky team car instead.
“Devastated to have to withdraw from this years TDF. Injured wrist and tough conditions made controlling my bike near to impossible,” he said on his Twitter feed.
Sky team manager Dave Brailsford said their attentions would now turn to Richie Porte.
“It’s not to be (Froome’s) year but in Richie Porte we’ve got a very capable guy who will now lead the team,” said Brailsford.
“I think like anything else, on a day like today when you have a setback, you’ve got to roll with it.
“It’s part of sport, you’ve got to recalibrate your goals and go again. You might take a punch but you get up and go again.”
Froome himself gave his backing to Porte and wished the Australian well for the rest of the Tour.
“Thanks to the team & support staff for trying to get me through today. Wishing @richie_porte & @TeamSky the best for the rest of Tour!” he added on Twitter.
Another Sky teammate, Geraint Thomas, said contingency plans had already been put in place before Wednesday’s gruelling 152.5km stage from Ypres in Belgium to Arenberg Porte du Hainaut that included 13km of cobblestones over seven sectors.
“We knew going into today we had Richie as well and it was a kind of two-pronged attack. They were both on an equal footing in the team,” he said.
None of the overall contenders, however, were on an equal footing with Nibali.
The Italian rode a stunning race and came home in third behind stage winner Lars Boom.
But while Boom, a former cyclo-cross racer, is a specialist on the cobbles, Nibali had hardly any previous experience.
Yet he handled the roads that normally grace the Paris-Roubaix one-day Classic with incredible ease.
“It was exciting, you’ve got to say that,” said a gracious Brailsford. “It might not have worked out for us but if you’re a bike fan and watched the way that Nibali rode today, that was pretty impressive.
“You know, fair play to him. I thought it was unbelievable the way he rode, to ride away from (Fabian) Cancellara and (Peter) Sagan on the cobbles, that was exciting and I think we’ll remember that for a long time.”
Nibali struck a blow to his rivals and now leads twice former winner Alberto Contador, who is 19th overall, by 2:37.
Other possible contenders such as world champion Rui Costa, Spaniard Alejandro Valverde and Americans Tejay Van Garderen and Andrew Talansky are all more than two minutes back, while Porte is probably the best placed of the potential winners at 1:54.
“It’s a good advantage over Contador but there’s a long way to go to Paris,” said Nibali.
“I have to stay calm and have a good race and a good strategy for the coming stages.”
A day after German Marcel Kittel won his third stage out of four, only to then see his country’s football team thrash hosts Brazil 7-1 to reach the World Cup final, Boom said he hoped there would be an omen there.
His country the Netherlands play Argentina in the second semi-final on Wednesday evening.
“For sure, I’ll watch the match and I hope we’ll win,” he said.
“I hope the Dutch win also 7-1, I know they’re really motivated. It’s a semi-final and I hope they do well.”