Sergio Floccari's early strike put the Biancocelesti on course for a third straight win that responded to Udinese's come-from-behind 2-1 triumph over Atalanta.
After Mauro Icardi spurned a series of chances to drag mid-table Samp back into the tie, Antonio Candreva converted a late penalty to ensure Lazio's gap to fifth place remains at two points ahead of next weekend's season-ending game at Cagliari.
Within seconds of the start Miroslav Klose was sniffing in Sampdoria's box after seizing on a Hernanes pass, but the ball ended up in the Stadio Olimpico crowd.
It did not matter, though, as Floccari found a way through in the 11th minute.
Klose was heavily involved as the German's shot ricocheted against Floccari's knee following a corner and span into the net.
Samp responded brightly, Icardi forcing a fine save from Federico Marchetti with a 25-yard rocket, but Lazio went closer to scoring a second goal in the 24th minute.
Klose and Floccari combined again to split the Samp backline but the Italian put his shot wide when one-on-one with Angelo Da Costa.
The minutes preceding the break brought a quickfire exchange of exciting chances.
First, Icardi slammed Gianluca Sansone's chested ball against the crossbar, thanks to a deflection off Giuseppe Biava, then Da Costa put gloves to a venomous effort from Candreva.
The Italy international was determined to make amends after the interval and his shot from range did shave paint off a post.
Samp took the hint and rallied to close ranks, with the more organised approach allowing Sansone to launch a cross into the Lazio box, but Icardi came up just short.
Home substitute Cristian Ledesma might have had better luck with his ball inside for Floccari but Da Costa squeezed the finish out to safety.
Marchetti repeated the trick on a daisy-cutter from Gianni Munari, who was then replaced by Renan, who would make a brief cameo in the capital city.
After the Brazilian promptly received his marching orders for dissent, Samp's afternoon took another turn for the worse as Daniele Gastadello conceded a penalty for his sloppy foul on Ogenyi Onazi.
Candreva stepped up to the spot and treated the Biancocelesti faithful to a cheeky chipped penalty that bamboozled Da Costa.