The yellow jersey from Astana crossed the finish line of the mountainous 145.5km stage 18 one minute and 10 seconds ahead of Frenchman Thibaut Pinot (FDJ), who moved into second place in the overall standings after Spain's Alejandro Valverde (Movistar) cracked on the last mountain-top finish of the race.
Provided he reaches Paris in one piece, Italian national champion Nibali - who leads Pinot by a huge 7:10 on GC - will be the first Tour winner to win four road stages since Eddy Merckx in 1974.
"It's a big gap and with more than seven minutes I'm feeling confident and a lot calmer ahead of the final stages and the time trial," said 29-year-old Nibali, a previous winner of both the Giro d'Italia and Vuelta a Espana.
Valverde dropped from second to fourth place as French veteran Jean-Christophe Peraud (Ag2R-La Mondiale) - who took fourth in the stage behind polka dot jersey Rafal Majka (Tinkoff-Saxo) and ahead of American Tejay Van Garderen (BMC) - rose to third place, just two seconds ahead of the Spaniard.
Stalemate on the preceding Col du Tourmalet meant Nibali and his rivals crossed the summit in one group with 50km left to ride. Valverde attacked on the long descent to join two Movistar team-mates involved in the early break. But fierce pace-setting by Nibali's Astana team-mate Jakob Fuglsang nullified Valverde's threat by the start of the final climb.
Nibali made his move early, attacking inside the last 10km following a move by the veteran American Chris Horner (Lampre-Merida), the rider who denied him a second Vuelta title last autumn.
Nibali swept up the remnants of the break before sweeping past lone leader Mikel Nieve of Team Sky with 8km remaining:
Behind, double stage winner Majka led the chase - eager to secure, if not a third stage win, then enough king of the mountain points to make the polka dot jersey his all the way to Paris:
An attack by Pinot, the white jersey, with 6km remaining was covered by Peraud and Van Garderen, but caught out both Valverde and French youngster Romain Bardet (Ag2R-La Mondiale).
Valverde combined with Bardet, Leopold Konig (NetApp-Endura) and Belkin pair Bauke Mollema and Laurens ten Dam as they fought to reduce their losses. But the Pinot trio rode a high tempo and soon caught Majka with 3km remaining.
Nibali - having earlier survived a minor scare when clipping a spectator distracted by her camera phone phone - pointed towards his Astana sponsors logo and punched the air as he crossed the line, peerless and fearless, to underline his utter dominance on the race.
"Today was not about the rankings - I just wanted another stage win," said a bullish Nibali, winner in Sheffield, La Planche des Belles Filles and Chamrousse.
"To win a stage in the Pyrenees is very important and I dedicate it to my whole team."
Majka attacked in the final kilometre but his move was covered by Pinot, who secured another mountain-top second place after crossing the line 1:10 down on Nibali and two seconds ahead of Majka. Peraud took fourth ahead of Van Garderen, both a further three seconds in arrears.
Bardet took sixth place ahead of Mollema, Konig and Haimar Zubeldia (Trek Factory Racing). A tiring Valverde was tenth place, 1:59 down on Nibali.
With Pinot, Peraud and Valverde separated by just 15 seconds on GC ahead of Saturday's decisive individual time trial - a rolling 54km from Bergerac to Perigueux - there is still everything to play for in the battle for podium positions in Paris.
TWENTY-MAN GROUP: Thursday's final stage in the Pyrenees was animated by an early group that featured Mikel Nieve (Sky), Jesus Herrada and Jon Izagirre (Movistar), Yuriy Trofimov (Katusha), Alessandro De Marchi and Marco Marcato (Cannondale), Lars Boom (Belkin), Jan Bakelants (OPQS), Blel Kadri (AG2R), Matthieu Ladagnous (FDJ), Daniel Oss (BMC), Bryan Coquard, Kevin Reza and Thomas Voeckler (Europcar), Julien Simon (Cofidis), Sylvain Chavanel and Marcel Wyss (IAM), Bartosz Huzarski and Tiago Machado (NetApp-Endura) and Florian Guillou (Bretagne-Seche).
After two Cat.3 climbs and an intermediate sprint won by Coquard, the leaders held a 3:30 advantage as they started the major test of the day, the mythical Col du Tourmalet. Chavanel launched the first attack, only to be shortly caught and passed by fellow Frenchman, the stage eight winner Kadri, and Spain's Nieve. Kadri crossed the summit of the Tourmalet in pole position to net the €5,000 Souvenir Jacques Goddet prize, named after the former director of the race.
The peloton crossed the summit of the climb first used in 1910 (when stage winner Oscar Lapize famously called the race organisers "assassins") with a gap of 4:35. But the advantage came tumbling down as Valverde lit the torch behind with his downhill attack.
On the hunt for Sky's first win of a miserable Tour, Nieve dropped Kadri at the outset of the final climb. But the Spanish climber, recovering from illness, had little over a minute to play with and stood no chance once Nibali decided to enter the history books.
RIDE OF THE DAY: The plaudits will go to Nibali but the stage was littered with fine performances - from Majka's polka dot-winning third place to the efforts of Frenchmen Pinot and Peraud in distancing Valverde on the climb to Hautacam.
DAY TO FORGET: Thomas Voeckler was part of the day's main break but the French veteran suffered mercilessly on the Col du Tourmalet to cap what has been a troubled Tour for the rider whose position as French favourite is very much a thing of the past.
COMING UP: The sprinters get a rare chance to shine on Friday's 208.5km stage form Maubourguet to Bergerac with a flat ride that includes just one categorised test - the Cat.4 Cote de Monbazillac. The climb peaks out at 7.6% and comes with 14km remaining - so expect some hefty jostling for positions by the teams of the main sprinters. Will Peter Sagan use this as a springboard, or will the Slovakian - still without a win - trust his kick to end the barren run?
STAGE IN A SENTENCE: Nibali secures Four de France as Frenchmen Pinot and Peraud leapfrog Valverde.
- Sports & Recreation
- Thibaut Pinot
- Alejandro Valverde
- Tejay Van Garderen
- Jean-Christophe Peraud
- Col du Tourmalet
- Rafal Majka