Sergio Floccari and a last-gasp Antonio Candreva penalty extended the Biancocelesti's winning run to three games and increased Samp's winless run to ten games.
There was a touching ceremony before the game for Cristian Brocchi, who retired on Friday after suffering a metatarsal injury back in February. Lazio were without Abdoulay Konko, Michael Ciani, Ederson and Stefano Mauri, but Ogenyi Onazi was rewarded for his midweek strike against Inter Milan by starting ahead of Cristian Ledesma.
Lazio hit the front after ten minutes. corner wasn't cleared, Stefan Radu flicked it on and Klose's shot was turned in off the post by the knee of Floccari. Giuseppe Biava was stood in an offside position, but wasn't interfering with play.
Halfway through the first half, Floccari spurned a chance to double the advantage. Klose threaded through, only to see the forward fluff his lines and loft the ball over the onrushing Junior Da Costa and wide of the post.
Da Costa beat away a vicious Candreva free-kick, before a last ditch Biava challenge thwarted Sansone from connecting with Andrea Poli's pull-back.
Radu had his nose busted open after a collision with Mauro Icardi and Federico Marchetti. Da Costa then bravely ran out to punch the ball clear from an advancing Klose.
Three minutes before half time, an Icardi snapshot deflected off Biava and rattled the crossbar.
Lazio were equally as dangerous going into the break. Hernanes sent an angled grasscutter into Da Costa's gloves, before the goalkeeper stayed alert to tip Candreva's lob onto the top of the net.
Candreva flashed a dangerous shot past the post at the start of the second half. Radu continued to spout blood from his nose and had to be substituted, while Sampdoria also lost Poli to a thigh injury.
Ledesma sent Floccari clear in the final ten minutes, but Da Costa ran out to close the angle and saved smartly with his feet.
Sampdoria pressed the self-destruct button in stoppage time. Substitute Renan Garcia was given a straight red card for dissent, before Daniele Gastaldello fouled Onazi in the box. Candreva stepped up and coolly chipped a Pirlo-esque penalty into the net, as a despairing Da Costa dived the wrong way.
Lazio: Marchetti; Gonzalez, Biava, Cana, Radu, (Dias 63) Candreva, Onazi, Hernanes, (Ledesma 51) Lulic, Floccari, (Kozak 87) Klose
Sampdoria: Da Costa, Gastaldello, Mustafi, Rossini, Rodriguez, Poli, (Obiang 71) Munari, (Renan 61) Maresca, Poulsen, (Berardi 46) Sansone, Icardi
Goals: Floccari 10 (L) Candreva pen 93 (L)
Sent off: Renan 91 (S)