Juventus’ job was made easier when Fabio Lucioni was sent off 31 minutes in.
From there, Dybala, Cristiano Ronaldo, who got his 23rd of the season, and Gonzalo Higuain put Juventus seven points clear of Lazio a top the Serie A table, though the Biancocelesti have played a game less.
At the other end, Lecce remain in the relegation zone, level on points with Genoa, but have played a game more.
After an early onslaught for Juventus, Lecce settled and had an early chance through Marco Mancosu, but he fired straight at Wojciech Szczesny from close range.
At the other end Rodrigo Bentancur, making his 100th Juve appearance, headed a Miralem Pjanic corner well wide, and a Adrien Rabiot screamer was well saved by Gabriel.
Things got more difficult for Lecce when Fabio Lucioni miscontrolled a pass and had the ball stolen by Bentancur, who, in on goal, was brought down by the Lecce No.5. That resulted in a red card for the defender.
However, that never stopped the Salentini side and Panagiotis Tachtsidis fired wide from the edge of the area.
Juventus should have taken the lead before half time, when an unmarked Cristiano Ronaldo headed over the bar from six yards.
Then Federico Bernardeschi blazed a Ronaldo cross over the bar from a similar position.
After the break, Juventus dominated proceedings as expected and Dybala curled an effort wide, before the Argentine picked out the top corner from the edge of the box.
A foul by Luca Rossettini on Ronaldo resulted in a penalty for Juventus, which the No.7 converted with ease to double Juventus’ lead.
Ronaldo was denied by a brilliant Gabriel save, with the Lecce goalkeeper also at hand to palm a Matthijs de Ligt effort wide.
Higuain made his return to the Juventus team and got on the scoresheet, picking up a Cristiano back heel and smashing into the net.