After getting their first victory of the season over Parma on Saturday they needed goals from Simone Missiroli, Sergio Floccari and Domenico Berardi to see off Empoli.
The victory lifts Sassuolo into 12th place in the Serie A table and into double figures for the season with 10 points, while Empoli remain on seven from their opening nine matches.
It was the visitors who opened the scoring, though, as Daniele Croce struck his first league goal of the season on 18 minutes.
Elseid Hysaj's cross from the right was miscued by Piotr Zielinski but the ball fell to Croce and he fired home from 12 yards.
Sassuolo were nearly level on three occasions before the break but the hosts wasted good openings each time.
The equaliser eventually came four minutes before the hour as Missiroli timed his run to perfection to get in between two defenders to tap home Saphir Taider's right-wing cross.
Berardi had the chance to put Eusebio Di Francesco's side ahead three minutes later from the spot, however, his effort clipped the top of the bar on its way over.
Sassuolo did not have to wait long for a second goal though, as Floccari fired a stunning long-range effort beyond Davide Bassi.
The home team secured the points on 73 minutes as Berardi made up for his penalty miss with a close-range header.
The 20-year-old headed home his third goal of the season after Nicola Sansone delivered a perfect cross to the back post.
‘After Manchester City’s recent form, maybe they’re the underdogs against Manchester United!’ Former Red Devils defender on this weekend’s derby
‘Arteta, Alonso, Emery, me… none of us were physical players – we needed the understanding of the game. That probably helped us move into management’: Premier League boss reveals reasons for natural career progression
