The Italy international netted twice to help Rudi Garcia's men to a comfortable home win, with Miralem Pjanic also finding the net.
Mattia Destro gifted the Giallorossi the lead in the closing stages of the first half, before Miralem Pjanic made it two after the break and Destro again struck to effectively decide the match.
The guests somewhat surprisingly started the match the better side, and Eder got a good chance to hand his side the lead midway through the first half. Angelo Palombo set up the attacker with a fine through ball, but he failed to beat Morgan De Sanctis.
Roma then took the initiative and got two chances to break the deadlock around the half-hour mark. First, Gervinho threatened after a good move, only for Daniele Gastaldello to come to the rescue for Sampdoria, before a good Pjanic shot was kept out by Angelo Da Costa.
De Sanctis was called into action again only minutes later as Lorenzo De Silvestri reached Roberto Soriano and the Roma goalkeeper showed his class with a fine save.
Kevin Strootman should have opened the scoring shortly before the break after some poor defending from Palombo, yet the Netherlands international only hit Da Costa from close range.
Roma did go ahead in the closing stages of the first half, though, via Destro. The striker beat his marker to the ball to meet a Alessandro Florenzi corner and left Da Costa no chance, making the score 1-0.
Rudi Garcia's men kept pushing for more after the break, and they did not need long to double their lead. The referee awarded the hosts a free kick in a dangerous position and Pjanic beat the Sampdoria goalkeeper with an accurate strike over the wall.
Things only got worse for the away side shortly after when Destro made it three for Roma. Gervinho reached the former Inter youngster with a low pass inside the area, and the striker had no trouble finding the net from close range.
Sampdoria was then reduced to 10 men toward the end of the game as Gastaldello was shown his second yellow card of the evening for a foul on Radja Nainggolan.
Roma sits second in the league table with 54 points from 23 games, trailing leaders Juventus by nine points, but with a game in hand.
The Giallorossi resume Serie A action on Saturday when they travel to Bologna.