The home side grabbed a goal at the death to condemn Juve to its first defeat of the 2014-15 Serie A season.
Genoa shocked Juventus 1-0 to hand the champion its first league loss since March and sour Gianluigi Buffon's 500th Serie A appearance.
Luca Antonini bundled the winner home from six yards in the 94th minute and, with just 20 seconds of stoppage time remaining, there was no way back for Massimiliano Allegri's men.
Genoa substitute Alessandro Matri - formerly of Juve - drew the attention of two defenders and crossed to the unmarked Antonini, who saw his unconvincing effort hit the back of the net despite the best efforts of the desperate visitors.
It was a cruel way for Buffon's milestone match to end as a tired Juve lost just its second league match of 2014.
Juve was twice denied by the woodwork on Wednesday, with Fernando Llorente firing into the base of the left post midway through the first half. Defender Angelo Ogbonna lifted over Genoa goalkeeper Mattia Perin in the 70th minute, but saw his effort hit the post after the host side was caught napping at the back.
And those close calls came back to haunt Juve - playing its fourth match in 12 days - as Antonini netted a dramatic winner.
Juventus now only tops the league on goal difference after second-placed Roma beat Cesena.
Buffon wore a special captain's armband that simply read '500' for a Juventus side which brought in Paul Pogba and Stephan Lichtsteiner, while Matri started on the bench for the host - despite scoring in its 2-1 win at Chievo on Sunday.
Carlos Tevez and Pogba shot wide from distance as halftime approached and the off-target efforts continued after the break - Lichtsteiner and Leonardo Bonucci the latest culprits.
Buffon made his first save of the night in the 64th minute, tipping a swerving Giovanni Marchese effort over the bar, while at the other end, substitute Alvaro Morata played in Tevez - only for him to smash over from 20 yards.
Morata forced a tidy stop from Perin from an acute angle in the 84th minute, and the goalkeeper went one better as the final whistle approached, reacting quickly to excellently tip another effort from the Spaniard over.
And Perin's saves proved crucial as Antonini's first league goal of the season gave Genoa a famous win.