The veteran centre-back bulleted an effort home to gain the Nerazzurri their first three points since December
The 35-year-old defender's strike came just after half-time, when he emphatically headed home from a corner to give goalkeeper Gianluca Pegolo no chance.
That earned a deserved win for Walter Mazzarri's side, who dominated for much of the game and perhaps should have had more than the one goal they scored.
In the end, though, it mattered little as they finally ended a poor run of form that had seen them pick up just two points from their previous five games and not win in any competition since December 22nd's victory over city rivals Milan.
Sassuolo started with six players signed in January, but the new-look nature of their side was not obvious early on as they pushed their more illustrious opponents back, Jonathan having had to head away a particularly dangerous cross.
Fredy Guarin then had Inter's first effort of note when he unleashed a long-range drive that had Pegolo scrambling to palm away.
Hernanes almost marked his first start with a spectacular goal after he profited from a poor defensive header from Paolo Cannavaro, but the Brazilian's fiercely curling effort whistled just wide of the top corner after 19 minutes.
Sassuolo could have taken the lead when Domenico Berardi’s dangerous free kick was met by Lorenzo Ariaudo after 24 minutes, but he could not keep his header down.
Berardi was instrumental in Sassuolo's last win - netting four against Milan - and he almost opened the scoring with a 30-yard free kick that was heading for the corner until Samir Handanovic made a superb flying save.
Diego Milito had two great chances for Inter late in the first half. First, Rodrigo Palacio's surging run ended with him setting up his fellow countryman, but Pegolo saved with his feet after Ariaudo's desperate block took the sting out of the shot.
An even better chance was passed up when Palacio sprung the offside trap and crossed to Milito, but he took a touch to control, which gave Pegolo time to smother his shot.
Inter did finally take a deserved lead after 47 minutes through the veteran Samuel, whose bullet header flew past Pegolo from Hernanes' set piece.
Sassuolo looked beleaguered and Pegolo almost put his team in further trouble when he punched straight to Jonathan, but he lashed wide when well placed.
The impressive Hernanes continued to threaten and his fierce drive was only stopped by the legs of Pegolo as Inter pushed.
The goalkeeper continued to keep his side in touch as he stood firm in the face of sustained pressure, but Sassuolo never looked like springing a surprise on the counter as Inter controlled matters.