On a sunbaked and melting Alpine road, the 29-year-old Italian, cemented his control of cycling's greatest race with a solo-finish victory that was an afterthought to gaining time on other title contenders.
Team Sky's Richie Porte, who began the day in second, saw his title hopes all but vanish after he lost about 9 minutes to Nibali on the last climb along the grueling 197.5-kilometre (122-mile) trek from Saint-Etienne to Chamrousse ski station.
Ever cautious, calm and understated after his stage win, Nibali noted that three big Alpine climbs still await Saturday and other punishing ascents are on tap in the Pyrenees next week.
"For the coming days, I only know that I have to remain quiet," he said.
But in the winner's circle, where he collected the yellow jersey for the 11th time this year, Nibali perhaps let slip a bit more happy emotion — knowing that a first Tour victory for an Italian since Marco Pantani in 1998 just got a little closer.
"I expect more attacks tomorrow in another very hard stage and next week," Nibali said. "My advantage over Porte is good now. He's the rider I feared the most in the closing time trial."
If Nibali's mountain dominance keeps up — on Monday, he won the only other high-mountain stage so far — the 54-kilometre (33-mile) time-trial in Stage 20 from Bergerac to Perigueux is the only real challenge left in his way.
The unexpected has gone Nibali's way. He surprised himself by winning an up-and-down Stage 2 stage in the hills and dales of Yorkshire and capturing his first Tour yellow jersey. He mastered cobblestone treachery in Stage 5, when 2012 Tour champ Chris Froome crashed out. And then, two-time Tour winner Alberto Contador went out five stages later after a fast downhill crash fractured his tibia.
In a sport where many dominant riders in past years later turned out to be drugs cheats, Nibali confronted the issue of doping a day earlier, saying he expected questions about it. "This theme belongs to the past," he said, crediting recent efforts like enhanced testing and the biological passport to clean it up.
This 101st Tour could become the third straight in which the winner locked up victory from before the halfway point. Last year, Froome was in yellow from the eighth stage onward. In 2012, Bradley Wiggins had the shirt for good after Stage 7.
Nibali took it in Stage 2, lost it in Stage 9, and regained it a day later. He's hoping to take it home after a largely ceremonial ride on the Champs-Elysees in Paris on July 27.
A comeback by a rival would be exceptional by recent standards. After the 13th stage last year, Froome had three other riders within minutes. In 2012, Wiggins had only two. After Friday's ride, no one is within three minutes of Nibali.
The first of two days in the snow-capped Alps lived up to its billing as the daunting final climb of 18 kilometres (12 miles) with an average 7.3 per cent gradient shook up the overall standings.
The ride was hot: black tar on the recently resurfaced road to Chamrousse melted. Big crowds lined the route, including fans dressed as superheroes and one as a scantily clad Borat — the Sacha Baron Cohen film character.
As riders embarked on the final climb, the pack was mostly together and Valverde's Movistar team was pushing the pace. But when it hit the steepest part, Porte struggled and dropped off the back and Nibali briefly turned his head to look. Valverde attacked a short while later, but Nibali and the others reeled him in.
Nibali said he felt "better and better" as he climbed, despite the heat of more than 30 degrees Celsius (86 F). When the Italian saw "Richie Porte in trouble," he turned his attention to gaining time on Valverde, he said.
After two riders raced ahead, the Italian leader struck — jumping out of his saddle, and pedaling while standing in the upright riding position known in French as "la danseuse" or the dancer. He overtook them, and went on to win.
Porte's troubles also meant others climbed in the standings: France's Romain Bardet moved up to third, countryman Thibaut Pinot was fourth, and American Tejay van Garderen fifth.
Nibali appeared to be taking a risk that his effort to distance his rivals could come back to haunt him. By his own admission a day earlier, he said that he feared the second Alpine day more.
Saturday's 177-kilometre (110-mile) stage takes riders over three tough climbs from Grenoble to Risoul — including the Izoard pass that is one of the hardest under cycling's ranking system.
Some of his rivals seem to be accepting that Nibali may win.
"Vincenzo is the strongest rider in the race, but after him, there is a place to take," Bardet said, referring to the final podium.
Nibali "played it well", said FDJ.FR team manager Marc Madiot. "Now he can say 'I've got all the cards, I can do what I want, when I want and if you try to slap me, I give two slaps in return.'"
Greg Keller contributed from Chamrousse, France.