Froome attacked about two-thirds of the way up the mammoth 21-kilometre Ventoux, and his brutal acceleration was too much for two-time former champion Contador. The Spaniard dropped back and finished about one minute 40 seconds behind. Colombian Nairo Quintana was second, 29 seconds behind.
"This is massive. Everyone wanted to win this stage today, on Bastille Day, being on top of Mont Ventoux," Froome said. "It really was an epic stage today."
The win means Froome effectively made up the time he lost on Friday's sprint stage, when Contador caught him out with a surprise attack.
"My objective today was to take a bit of time in the general classification, but I didn't think I could win the stage," Froome said. "I thought Quintana would win it. But then his legs started to go in the last two kilometres."
Ventoux is one of the most famed climbs in the Tour's 110-year history. Britain's Tom Simpson collapsed and died on it during the 1967 Tour.
Froome raised his right arm in the air when he clinched his second stage win of the race after winning a mountain stage in the Pyrenees on stage 8 with a similarly effective attack.
"It was incredible today, incredible. This is the biggest victory of my career," Froome said. "This climb is so historical. It means so much to this race, especially being the 100th edition. I really can't believe this."
He now leads Dutchman Bauke Mollema by 4 minutes, 14 seconds and Contador by 4:25.
"It wasn't really about sending (Contador) a message but I'm obviously going to take as much time as I can," Froome said. "I'm really happy to have this advantage now."
The longest stage of the race took riders over 242.5-kilometres from Givors in the winemaking Rhone Valley and ended in the Provence region.
A nine-man breakaway group led early on, including sprint champion Peter Sagan, who has a massive lead in the green jersey competition for sprinters, and French veteran Sylvain Chavanel.
Touted as one of cycling's showmen, Sagan lifted his front wheel and did a wheelie, followed by a salute to the crowd in a rare moment of frivolity on a bitterly hard day.
Froome said he needed "five or 10 minutes on the oxygen" mask after the stage.
The small group of front-runners split open on Ventoux, leaving Chavanel alone in front.
Andy Schleck, the 2010 Tour champion, was dropped straight away while the 36-year-old Cadel Evans, the 2011 winner, then faded along with Chavanel.
"It was a terrible day for me," Evans said.
With about 15 kilometres to go. Froome, meanwhile, only had two Sky teammates — Australian Richie Porte and Britain's Peter Kennaugh — to help him.
Then Quintana surged ahead. He attacked Froome four times on the last climb in the Pyrenean mountains on stage 9 up to Bagneres-de-Bigorre, but could not beat him.
It proved to be the same story this time.
"We talked a little bit. I was just trying to motivate him," Froome said. "I was telling him 'Come on man, keep pushing.' But in the last 2k he just couldn't really hold the wheel anymore."
At one point, Contador still had three teammates with him but Froome would lose Kennaugh shortly after, leaving just Porte.
Then the yellow jersey group blew wide open. Suddenly, Froome and Porte were alone with Contador.
With seven kilometres to go, Froome launched a devastating attack on Contador — rocketing up the slope as fans threw water over him and others lit orange flares or waved British flags close to his face.
As he moved alongside Quintana — who had a nose bleed during the climb — Froome launched a second brutal acceleration.
"I needed more strength but I couldn't find it," Quintana said. "I'd already made an enormous effort."
Victoria cyclist Ryder Hesjedal is 66th after finishing the stage 114th, one ahead of David Veilleux of Cap-Rouge, Que. Svein Tuft of Langley, B.C., was 166th in the stage.
Tens of thousands of people crammed the roadside on July 14 — France's national day.
Other countries were well represented, though.
There were dozens of Union Jacks and Norwegians and Danes wearing Viking costumes. Pockets of Belgians and Dutch swigged beers, others dressed up as animals or ran alongside the riders in inflatable body suits.
"I was amazed to see so many British people there," Froome said.
The chaotic, raucous, deafeningly loud scene saw race motorbikes and spectators perilously close to the riders.
Near the summit, the scenery started to change, with fewer and fewer trees; then just a little bit of green brush left, before even that gave way to the barren, lunar landscape that makes Ventoux unique.
Following Monday's rest day, there is a medium mountain stage on Tuesday, and then three straight days of tough climbing in the Alps.