Despite playing much of the second half with 10 men, Lazio managed to record back-to-back Serie A victories for only the second time this season. Edy Reja's side is now just two points off a Europa League place.
Antonio Candreva put the Biancocelesti ahead, before Lucas Biglia saw red early in the second half. Sampdoria failed to make their numerical advantage count and Senad Lulic punished them by adding a second to seal the victory.
Helder Postiga was given a first Serie A start after a late injury ruled out Miroslav Klose. Etrit Berisha took the goalkeeping gloves from another injury victim Federico Marchetti. Cristian Ledesma was suspended, while Biglia had recovered quicker than expected from a rib injury to start in midfield.
Sampdoria hadn't won this fixture since 2005. Sinisa Mihajlovic began a touchline ban, so his assistant Nenad Sakic gave the instructions from the touchline. Captain Daniele Gastaldello missed the trip through injury, but Vasco Regini returned from suspension.
The sun was out in Rome, but neither team shined in the opening quarter. It took 15 minutes for either goalkeeper to be seriously tested. Angelo Da Costa ran out to catch a Candreva cross, before the winger blazed over from a wide position. Regini ran across to dispossess Keita Balde in the box after the teenager had ran clear.
Samp caused problems from two set pieces. Maxi Lopez struggled to control an Angelo Palombo free kick and ran into Lazio traffic, before an unmarked Manolo Gabbiadini couldn't keep his shot down after collecting a short corner. Berisha flapped at a Palombo corner, struggling to punch the ball clear, but Lazio managed to clear their lines.
Candreva finally forced a save from Da Costa on half an hour. The Lazio man gathered Ogenyi Onazi's through ball deep inside the Sampdoria box and stung the goalkeeper's palms at the near post. Five minutes before the break, Keita's shot took a deflection and looped into the air, forcing Da Costa to run out and punch clear from the advancing Lazio players.
Lazio hit Samp with a sucker blow three minutes before half time. Keita used his trickery to bamboozle Gaetano Berardi, before rolling the ball across the box for Candreva to turn a low shot into the far corner.
Keita broke clear in stoppage time. However, Palombo's well timed challenge was enough to take the sting out of the shot and the ball went out to safety.
Six minutes after the break, Candreva fed Postiga in a promising position. The Portuguese striker wanted one touch too many and was dispossessed by Gabbiadini and Palombo. At the other end, Berisha comfortably parried a Gabbiadini free kick over the bar.
The visitors lost Gabbiadini to a shoulder injury, while Lazio went down to 10 men. Biglia was dispossessed in midfield and hacked down Nenad Krsticic to pick up a second booking. Eder's resulting free kick was charged down and Berisha comfortably caught a Palombo effort from distance.
Regini almost turned into his own net when Lazio sprung a quick counter attack. Keita's burst of pace and subsequent cross was intended for Stefano Mauri, but the Samp defender stuck out a boot and deflected the ball inches past his own post. At the other end, Berisha was at full stretch to push clear an effort from Gianluca Sansone.
Samp's failure to use their one-man advantage was punished when Lazio put the game beyond them on 73 minutes. Onazi was crowded out by the corner flag, but still managed to play in Mauri. The substitute cut the ball back for Lulic to run in and blast his shot into the roof of the net.
Renan Garcia almost reduced the arrears for the visitors. The substitute's effort took a deflection off Abdoulay Konko and the ball rolled dangerously across the Lazio box with no Sampdoria player able to divert it into the net.
Joseph Minala, 17, was given his Lazio debut late on and Keita was cautioned for simulation in the area. Lorik Cana ran out of steam after running box to box in an effort to make the game safe. The visitors kept pushing forward. Eder was denied a penalty and Giuseppe Biava cleared Roberto Soriano's header off the line after Berisha failed to claim a corner.
Stefano Okaka went down under Onazi in the box, but the referee played the advantage and Renan fired the rebound straight at Berisha. Palombo curled one final free kick wide in stoppage time.
Lazio: Berisha; Konko, Biava, Cana, Radu; Onazi, Biglia, Lulic; (Minala 77) Candreva, Postiga, (Mauri 61) Keita (Perea 88)
Goals: Candreva 42, Lulic 73
Sent off: Biglia 57
Sampdoria: Da Costa; De Silvestri, Mustafi, Regini, Berardi; Palombo, Krsticic; (Renan 74) Gabbiadini, (Sansone 57) Eder, Soriano; Maxi Lopez (Okaka 61)