Duvan Zapata broke the deadlock with a low drive just after the hour mark and then teed up Marek Hamsik for the crucial second goal before Dries Mertens saw red for a poor tackle
Duvan Zapata opened the scoring for the home side shortly before the hour mark, and Marek Hamsik made it 2-0 nine minutes later.
Dries Mertens saw red for a poorly timed challenge almost immediately after Napoli's second, but Rafael Benitez's men held on to close in on faltering Roma, who have one win from their last seven league matches.
The match did not get off to the best of starts for Sassuolo, who saw defenders Luca Antei and Paolo Cannavaro - back at the club he represented for eight years until 2014 - forced off through injury in the opening 23 minutes.
The visitors could have been forgiven for taking a while to adjust at the back, but their defence saw out the first half without conceding.
Having dominated possession and chances in the first half, Napoli finally took the lead in the 61st minute, when Zapata stumbled his way through some questionable Sassuolo defending to convert a low effort.
Hamsik doubled the advantage soon after with a curling strike after being teed up by Zapata, but the home side saw Mertens sent off soon after.
The Belgian attacker had only been on the pitch five minutes when he was dismissed for a clumsy tackle from behind on Simone Missiroli.
Francesco Magnanelli saw a superb strike from outside the penalty area tipped wide by goalkeeper Mariano Andujar as Sassuolo looked to make their numerical advantage count, but Napoli held on for a comfortable win - Jose Callejon skewing wide a glorious opportunity to make it 3-0 late on.