The Argentine netted a second-half brace to secure a memorable win for the visitors, who had fallen a goal and a man down during a torrid opening 45 minutes
Sebastian Giovinco opened the scoring from the penalty spot in the first half, after Claudio Marchisio had been brought down by Gaetano Berardi, who later saw red for a second bookable offence.
However, Mauro Icardi netted a second-half brace to secure a memorable win for Riccardo Garrone's side that saw the Turn outfit lose their first game of 2013.
The hosts began the brighter of the two sides and it took Sergio Romero to deny Juventus an early goal, the Sampdoria goalkeeper smothering at the feet of Giovinco after initially hesitating to come and claim 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.
At the other end, Andrea Poli looked to test Gianluigi Buffon after the Juventus backline failed to clear their ranks. His effort, however, was weak and comfortably dealt with by the veteran shotstopper.
The Italian's shot appeared to shake the hosts into action and they came close to opening the scoring 20 minutes in, Romero expertly denying Giovinco with a strong right hand despite diving the wrong way.
However, the Blucerchiati shot-stopper was unable to prevent the Juventus attacker from netting minutes later, Giovinco tucking into the bottom left corner from the penalty spot after Marchisio had been felled by Berardi.
The Turin outfit thought they'd doubled their advantage on the half-hour mark when Andrea Pirlo's corner appeared to have been scrambled over the line by Alessandro Matri, but Romero did well to prevent a goal.
The afternoon went from bad to worse for Riccardo Garrone's side in the last 15 minutes of the half, though, after Berardi saw yellow for the second time following a lunge on Andrea Barzagli.
Juventus felt they had a shout for a second penalty after Matri was hauled down in the box by Angelo Palombo, only for the referee to blow for a Sampdoria free kick.
The visitors came excruciatingly close to finding a equaliser on the brink of half-time after Marcelo Estigarribia brushed Buffon's post with a curling free kick, leaving the Italian rooted to the spot.
Antonio Conte's side looked to double their advantage after the interval, but it was Sampdoria who netted early into the second half. Icardi fired a half-volley goalbound and Buffon proved unable to prevent the ball from squeezing past him and into the back of the net.
Poli went close on the hour mark to firing the visitors in front, but struck his volley into the ground and out for a goal kick, before Eder fired straight at Buffon after some good work on the edge of the 18-yard box.
Juventus were toothless in the attack and were 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 goal-line before the Blucerchiati managed to clear the danger.
The Montenegro international poked just inches wide from two yards moments later as Juventus pushed for 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, meaning the home side remain just five points clear of Lazio, who defeated Cagliari the night before.