A first win in three outings for the Neroverdi was sealed early on thanks to three first-half goals.
The opener arrived with just eight minutes on the clock, as Francesco Acerbi smartly turned home a flick-on from a central position.
Sergio Floccari doubled Sassuolo's advantage from a near-identical position, this time latching on to a cross from the right before turning and rifling home off the bar.
Any hope an out-of-form Sampdoria had of finding a route back into the game soon evaporated when Lorenzo Pellegrini tucked away at the second time of asking from close range for a quick-fire third.
Matteo Politano came closest to extending his side's advantage in the second half, but the hosts did have something to cheer when Ervin Zukanovic headed home Carlos Carbonero's cross for a late consolation.
Sassuolo are now just one point and one place behind champions Juventus, while Vincenzo Montella's men remain just two points above the drop zone. body check tags ::