- Romelu Lukaku (41', 89')
- Ruan (55' OG)
- Lautaro Martínez (58')
- Matheus Henrique (63')
- Davide Frattesi (77')
Lukaku, Lautaro Martinez and Sassuolo defender Ruan Tressoldi's own goal put the hosts three goals up by the hour mark but the visitors pulled two goals back to keep Inter on their toes until Lukaku sealed the win one minute from time.
Inter consolidated their position in the top four as they moved on to 66 points, one ahead of fourth-placed Lazio and five more than neighbours Milan who suffered a shock 2-0 loss at Spezia on Saturday to remain fifth.
"It was an opportunity not to be missed," said Inter assistant coach Massimiliano Farris.
"We wanted to put a cushion because we still have so many important games: the Champions League semifinal, the Coppa Italia [final].
"Today the [other] results gave us a chance to go all the way and we did very well."
Each team had an effort ruled out for offside in a lively start to the game and Lukaku sent a shot narrowly wide before the Belgian striker made space and arrowed a long-range shot into the net to give Inter the lead.
Sassuolo started the second half poorly when Tressoldi doubled Inter's lead with an own goal as he tried to intercept Raoul Bellanova's cross.
It was 3-0 three minutes later when Martinez netted from distance, a shot which was deflected off the unfortunate Tressoldi.
Lukaku, celebrating his 30th birthday, has had eight goal contributions in his last four league games, scoring five times and making three assists.
"Whenever we play at home with Sassuolo they always give us a lot of trouble. Last year we lost," Lukaku said.
"Today was important because we could get closer to Champions League qualification. We have won many games this month, we are well and we want to continue like this."
Inter, who have extended their season's longest winning streak to seven games across all competitions, face Milan in the second leg of the Champions League semifinal on Tuesday before they travel to champions Napoli.
Sassuolo, 13th on 44 points, host Monza on Friday.
- Matteo Marcenaro