Leonardo Mancuso scored to secure a surprise 1-0 victory for newly-promoted Empoli in Turin that left Juventus stunned and still without a win in Serie A this season.
Mancuso ended his side's five-game run without a league goal at Juve in the competition as he opened the scoring from close range, while Guglielmo Vicario impressed in goal.
Without Cristiano Ronaldo as he edges closer to returning to Manchester United, Juve's main attacking threat came through Federico Chiesa, but even he could not steer any of his three attempts past the Empoli goalkeeper.
Chiesa forced early saves from Vicario, with surging runs creating both opportunities before the goalkeeper produced smart saves to parry away.
However, it was Mancuso who struck first, profiting from Nedim Bajrami's deflected shot to spin and volley past Wojciech Szczesny.
Mancuso's opener stunned the vociferous Allianz Stadium and was Empoli's first Serie A away goal against Juventus since Sergio Almiron netted in January 2006.
Vicario pushed away another low effort from Chiesa, while Patrick Cutrone almost made it two but fired narrowly wide to Szczesny's right with a thumping effort.
On the stroke of half-time, Szczesny was called into action once more, retreating quickly to tip over the crossbar and spare Chiesa's blushes after the Juventus forward had looked to head backwards.
Paolo Dybala started the second half encouragingly, linking up with Alvaro Morata and drilling at Vicario before Bajrami forced another save from Szczesny.
Dybala curled wide from a free-kick, but the hosts failed to find a way past Vicario, ensuring a memorable victory for Empoli.