The iconic 34-year-old rider's dream of a fifth Tour de France title lay in tatters when a gust of wind caught his front wheel, hurtling him into a wall towards the end of a 'recon' before the Criterium's fourth stage time trial.
Team Ineos doctor Richard Usher said in a statement: "Chris was taken to Roanne Hospital where initial examinations confirmed multiple injuries, most notably a fractured right femur and right elbow.
"He has also suffered fractured ribs.
"He is now being airlifted to St Etienne University Hospital for further treatment."
Team Principal Dave Brailsford stated the priority now was to ensure "Chris gets the very best possible care, which he will do, so he can recover as soon as possible."
Brailsford said that the four-time Tour de France winner had worked "incredibly hard to get in fantastic shape and was on track for the Tour, which unfortunately he will now miss."
He added: "Even though we all recognise the risks involved in our sport, it's always traumatic when a rider crashes and sustains serious injuries.
"One of the things which sets Chris apart is his mental strength and resilience – and we will support him totally in his recovery, help him to recalibrate and assist him in pursuing his future goals and ambitions."
Brailsford said Froome had been speeding downhill with Dutch teammate Wout Poels when crashing.
"They were going very fast and the wind got his front wheel and sent him straight into the wall," Brailsford told French television.
The accident took place on a narrow descent through the village of Saint-Andre d'Apchon in the Loire region and other competitors on the recon estimated he would have been travelling at 60km/h (38 mph).
"He could hardly speak. He'll be helicoptered to either Lyon or Saint-Etienne hospital within a few minutes," said Brailsford at the scene where Froome received treatment in a parked ambulance.
This year's Tour de France embarks from Brussels on July 6 and the loss of a rider of Froome's stature will shake up ambitions at several teams.
Tour de France director Christian Prudhomme was swift to wish Froome a speedy recovery.
"We hope he gets well soon. The Tour de France won't be the same without him. Chris Froome has been the central character at the Tour since 2013," he said.
"His withdrawal changes the whole thing. Even if they have the title holder Geraint Thomas and let's not be lured into underestimating Egan Bernal, who will be his lieutenant or possibly more," Prudhomme said of two key Ineos riders.
French climber Romain Bardet, who came second to Froome on the 2016 Tour de France, described the news of the extent of his fellow rider's injuries as "dreadful".
"I didn't realise it was that serious," Bardet said when told after the time trial won by Wout van Aert.
"It's never nice when one of your rivals gets unlucky like that."
This year has been disappointing for Froome. He trailed in 91st in the Tour of Colombia, 94th at the Tour of Catalonia, 11th in the Tour of the Alps and 13th at the Tour de Yorkshire, leaving critics lukewarm over his 2019 Tour de France chances.
The Kenyan-born Froome, who at his best combines top level time-trialing skills with a fearsome prowess for climbing, first won the Tour in 2013 with Team Sky.
He went on to further Tour de France wins in 2015, 2016 and 2017. He also won the 2017 Vuelta a Espana and the 2018 Giro d'Italia, making him the greatest Grand Tour rider of his generation.