Sebastian Giovinco opened the scoring from the penalty spot in the first half after Claudio Marchisio was brought down by Gaetano Berardi. Mauro Icardi netted a second-half brace to secure a memorable win for Riccardo Garrone's side that saw the Turn outfit lose its first game of 2013.
The hosts began the brighter of the two sides, and it took Sergio Romero to deny Juventus an early goal, as the Sampdoria goalkeeper smothered at the feet of Giovinco after the Argentine initially hesitated from a low cross.
The pint-sized Bianconeri star came close to netting the opener minutes later after Simone Padoin pulled back for the striker, who fired just over from the edge of the 18-yard box.
However, the Blucerchiati shotstopper was unable to prevent Giovinco from netting minutes later, tucking into the bottom left corner from the penalty spot after Claudio Marchisio was brought down by Gaetano Berardi in box.
Juventus thought it had doubled the advantage on the half hour mark after a corner had been won. Andrea Pirlo's cross appeared to have been scrambled over the line, but Romero did well to prevent the goal. The afternoon went from bad to worse for Riccardo Garrone's side in the last 15 minutes of the half after Berardi was sent off for a second booking following a lunge on Andrea Barzagli.
Even so, Sampdoria netted early into the second half to pull level. Icardi fired a half-volley goalbound with Buffon unable to prevent the ball from squeezing past him and into the back of the net.
Despite the man advantage, Juventus was toothless in the attack and was made to pay with 20 minutes remaining. Icardi was played in by Pedro Obiang and the Sampdoria front-man smashed past Buffon from an acute angle.
The hosts looked for an instant reply and came close to dragging themselves back into the encounter after substitute Mirko Vucinic blasted against the cross bar and onto the goalline before the Blucerchiati managed to clear the danger.
The Montenegro international poked just inches wide from two yards moments later as Juventus pushed for their second goal and the equaliser. Padoin fired a stinging effort at Romero, fumbling his effort but the Sampdoria goalkeeper managed to pounce on the ball before Vucinic could tap home as the visitors secured a surprise win at the Juventus Stadium.