Dybala showed his class with a great finish but was forced off midway through the first half three days before a Champions League clash with Chelsea, having seemingly sustained a muscular problem.
Leonardo Bonucci doubled Juve's lead from the penalty spot, but Maya Yoshida's header gave Samp hope just before half-time at the Allianz Stadium on Sunday.
Manuel Locatelli's first goal for the Bianconeri gave them breathing space and although Antonio Candreva's strike set up a tense finale, the Turin giants secured a back-to-back Serie A home wins – and their first at home this season – in boss Allegri's landmark match.
Dybala put Juve in front with a fine finish in the 10th minute, rifling into the bottom-right corner with his left foot from outside the penalty area after Locatelli had set him up.