The Argentina international produced a superb performance at MAPEI Stadium on Sunday to inspire his side to a fourth victory in four league games and return to the top of the table.
Sassuolo had not lost at home since April but their chances of springing a surprise were dealt a blow just 16 minutes in, as Dybala brilliantly swept home his 50th goal for the club.
The 23-year-old scored five goals in his first three league games and struck again shortly after the interval to put Juve in control, expertly prodding home from a Juan Cuadrado pass.
Matteo Politano hit back two minutes later, scoring from close range after the returning Giorgio Chiellini prevented Claud Adjapong's effort from crossing the line, but a sublime Dybala free-kick made the points safe.
Juve climb back above Inter, who are also on 12 points following Saturday's win over Crotone, while Sassuolo remain just a point above bottom-club Benevento.
Andrea Consigli was twice called upon to keep out Juve in the first 10 minutes, making a flying save to his right to deny Miralem Pjanic before reacting superbly to block Gonzalo Higuain's volley from close range.
But Consigli was powerless to stop Dybala putting the visitors ahead in the 16th minute. Fit-again forward Mario Mandzukic sent a low pass into Dybala's path and the Argentina star swept a curled first-time strike into the bottom-right corner from 20 yards out.
Sassuolo looked bright going forward, with Politano testing Gianluigi Buffon, but they looked exposed to the Juve counter-attack and a better finish from Higuain after Dybala and Cuadrado combined would have made it 2-0 before the break.
The home side finished the half in encouraging fashion but, four minutes after the restart, they were undone by more Dybala brilliance.
Cuadrado fed the forward just inside the penalty area and, when it looked as though he had no route to goal, he produced an impudent toe-poke finish into the bottom-right corner.
The visiting fans were in full voice but Sassuolo hit back two minutes later, Politano converting from point-blank range after Adjapong had prodded the ball beyond Buffon at the keeper's right-hand post and forced Chiellini to cover on the line.
The resistance was short-lived, though. Having earned a free-kick 20 yards out, Dybala stepped up and whipped a fine finish past Consigli to complete his hat-trick just past the hour mark.
Blaise Matuidi went close with a volley and Cuadrado saw a late chance for a fourth deflected over, but the day belonged to Dybala, who was replaced to a standing ovation in the closing minutes after taking his tally for the season to 10 goals in six appearances in all competitions.
