Thiago Motta was forced to change his line-up shortly before kick-off after Andrea Cambiaso injured himself in the warm-up, with Charalampos Lykogiannis replacing him in the starting XI.
There were few chances for either side in a cagey opening 20 minutes, but Bologna goalkeeper Lukasz Skorupski was called into action just after the midway point in the half to make a fine save to deny Andrea Pinamonti at his near post.
Soon after that important stop, Bologna broke the deadlock in style. Michel Aebischer diverted Jhon Lucumí’s sumptuous cross past Andrea Consigli with a sublime, one-touch finish to give Motta’s side a slender lead at the break.
Bologna had been in this position many times before, though, having previously lost 17 points from winning positions this campaign - not only the highest number in Serie A, but also across Europe’s top five leagues.
Those fears were eased when Marko Arnautovic doubled their advantage with a cool finish, firing past Consigli with his third touch inside the box following Roberto Soriano’s perfectly timed through ball.
It was the Austrian’s eighth goal of the season and seemed to knock the stuffing out of Sassuolo. Lewis Ferguson provided the icing on the cake with a beautifully caressed strike after a neat one-two with Nicolas Dominguez.
The result sees Alessio Dionisi’s side succumb to a fourth successive away defeat - their worst run on the road in three years - and drop one place in the table to 14th.
Meanwhile, the three points were a perfect tonic for Bologna, who responded in fine fashion after a 6-1 humbling away at Internazionale to head into the FIFA World Cup break on a high.
Flashscore Man of the Match: Lewis Ferguson (Bologna)