The 37-year-old Quagliarella capitalised on poor marking by Lazio to head in from Tommaso Augello's cross in the 32nd minute after Samp had taken control of the game.
Augello added the second himself nine minutes later when a clearance landed at his feet and he thumped a left-foot shot into the net from the edge of the area for his first Serie A goal at the age of 26.
Lazio were missing a number of players including suspended forward Ciro Immobile, Serie A top scorer last season, but at least came to life for a spell in the second half.
However, they failed to take their chances and substitute Mikkel Damsgaard wrapped the game up for Sampdoria in the 74th minute after the ball ricocheted around the Lazio area.
Lazio, fourth last season, were left with only four points from four games while Claudio Ranieri's Samp side have six. (Writing by Brian Homewood; editing by Ken Ferris)