Juventus's Serie A unbeaten run came to an end after 49 matches on Saturday when Diego Milito's double helped Inter Milan win 3-1 in a pulsating 'Derby of Italy' clash in Turin.
The win leaves second-placed Inter one point behind champions and league leaders Juve and is a sign that Andrea Stramaccioni's side are genuine challengers for the title.
"It hurts to lose, obviously it hurts, but it's right to give credit to Inter, who played in a very intelligent way, with a great will to win," said Juventus captain Gianluigi Buffon.
"I conceded three goals without having all that much to do but that can happen against the players that Inter have, they're very good."
Juve scored straight from the kick off when Kwadwo Asamoah latched onto Mirko Vucinic's through ball and scuffed his shot into the path of Arturo Vidal, who gleefully tapped home from the edge of the six yard box after 19 seconds.
Television replays showed Asamoah was offside when he collected Vucinic's pass but the linesman's flag stayed down.
"We were caught napping for the first goal, even if it was offside, but after that we reacted and played brilliantly. We deserved to win," Milito told Sky Sport Italia.
"It was a really hard match. We knew that it would be like that, we were up against the current champions, a great team like Juventus."
Juve could have doubled their lead after eight minutes when Claudio Marchioso met Andrea Pirlo's delightful through ball with a volley that Samir Handanovic did well to push wide.
Inter must have expected a torrid evening but were unlucky not to level three minutes later when Rodrigo Palacio's header from Esteban Cambiasso's freekick was ruled out for offside.
Inter were giving Antonio Conte's side their toughest game yet but Handanovic saved them from ending the first half two goals down, saving from Vidal who was clean through on goal.
Inter wasted a golden opportunity to equalise eight minutes after the break when Palacio finished a three-on-two counter attack by shooting over the bar from close range.
They went close again three minutes later when Yuto Nagatomo forced a fine save from Buffon after dribbling past two defenders in the box, but Andrea Stramaccioni's side got the equaliser they deserved just before the hour mark.
Milito was clearly pulled back in the box by Marchisio as Inter worked a smart free-kick routine close to goal and the forward stepped up to smash the resulting penalty past Buffon.
The Argentine piled on the agony for the champions with a quarter of an hour left when Fredy Guarin's powerful shot was pushed straight into his path by Buffon, who could only watch as Milito gobbled up the chance to make it 2-1 to the visitors.
Stramaccioni substituted the striker in a bid to protect the lead and Pirlo nearly took advantage after 83 minutes when his long-range effort was pushed wide by Handanovic.
Nicklas Bendtner came close to his first Juventus goal two minutes later when he raced onto a misplaced Walter Gargano back pass and watched his chip sail just wide of the far post.
However Inter were always dangerous on the break and put the match to bed with a minute to go. Palacio collected Nagatomo's deft through pass and slipped the ball under Buffon to warn the rest of Serie A that Inter are here to stay this season.
"Inter were at the top of their game right until the end, and we accept this defeat... fundamentally credit has to be given to Inter," said Juve assistant manager Angelo Alessio.
Juventus won last season's title without losing a match and had last suffered defeat in the league against Parma in the penultimate round of the 2010/11 season.
The overall Serie A undefeated record run was put together by AC Milan in the early 1990s - 58 games, started against Parma and finished by the same team.
Earlier, AC Milan's Bojan Krkic scored his first goal for the club since moving from Barcelona in August as they cruised to a 5-1 home win over lowly Chievo.
The victory came courtesy of Milan's best performance by far this season and moved them up to seventh on 14 points and relieves the pressure on manager Massimiliano Allegri.
Milan, who have never lost to Chievo at the San Siro, took the lead after 16 minutes through Urby Emanuelson's stunning left foot half-volley from the edge of the area.
But Chievo, who had lost 11 games in a row to Milan going into the match, equalised two minutes later when Sergio Pellissier headed past Christian Abbiati from a corner.
Chievo fell behind 10 minutes before halftime when the impressive Riccardo Montolivo finished off a smart passing move by firing home a superb shot from nearly 20 metres.
Bojan extended the home side's lead after 41 minutes with his first Milan goal when his long-range strike was deflected past the despairing Sorrentino by Dario Dainelli.
With 15 minutes left Serie A top scorer Stephan El Shaarawy tapped home his eighth goal of the season.
Giampaolo Pazzini put the icing on the cake in added time when El Shaarawy laid the ball on a plate for him to provide the perfect ending to a rare happy evening for Milan this season.