Blerim Dzemaili and Lorenzo Insigne scored the goals for Rafael Benitez's men, who beat AC Milan 3-1 and Roma 3-0 over the past seven days and appear to have hit form ahead of their trip to Swansea in the Europa League on Thursday.
Sassuolo tried to find a route back into the game while Gonzalo Higuain left the field with an injury, giving Benitez some cause for concern, despite Napoli's latest victory.
Benitez fielded his strongest side, resisting the temptation even to rest Higuain in view of Thursday's trip to Wales, showing how much he still wants to clinch second spot in Serie A this season, a position which would earn them a direct place in the group stage of next season's Champions League rather than a place in the play-offs.
It took them a while to impose themselves on the game with Sassuolo showing how they had frustrated the Azzurri in Naples earlier this season.
After half an hour, Higuain wasted the first big chance of the game before Insigne was denied by Gianluca Pegolo.
Napoli finally found a way through in the 37th minute with Dzemaili finding the bottom right-hand corner from the edge of the area.
They doubled their lead 10 minutes into the second half when Paolo Cannavaro stood off Insigne, allowing him to progress into the area before curling a shot into the far corner. It was a gift from the former Napoli defender.
Insigne missed several chances to make it three before Dzemaili hit the crossbar.
Sassuolo tried to find a way back into the game with Simone Zaza twice going close, and they appeared to worry Benitez enough to send on an extra midfielder with Higuain taken out of the firing line after being fouled repeatedly.
He appeared to limp his way back to the bench and Benitez will be hoping he will be fine for Thursday,.