The Nerazzurri have been in a rich vein of form of late, with Sunday's triumph at the Stadio Atleti Azzurri d'Italia their third successive win, following on from triumphs against Chievo and Lazio, which have taken them well clear of the bottom three.
Carlos Carmona opened the scoring after 36 minutes, with Samp finding themselves two down before half-time when Giacomo Bonaventura headed home unmarked, while German Denis ensured there was no way back just before the hour mark.
It was the Argentinian who carved out the first chance of the match for compatriot Maximiliano Moralez, who fired wide from the edge of the box.
Samp made a decent start, but their finishing let them down with both Manolo Gabbiadini and Eder blazing over, while at the other end Denis continued to cause problems for the visitors, but his header also missed the target.
The visitors went closest to breaking the deadlock when Roberto Soriano's point-blank header was magnificently saved by Atalanta goalkeeper Andrea Consigli, who then tipped over another close range effort from Vasco Regini.
It was to prove a costly miss as the hosts made the breakthrough after 36 minutes when Denis played through Carmona, who slotted past Samp custodian Angelo Da Costa with a first-time shot.
Atalanta then doubled their lead six minutes later when Luca Cigarini's corner was headed home at the far post by an unmarked Bonaventura.
Soriano tried his luck from the edge of the area at the start of the second half but Consigli was equal to it before Samp's task of coming away from Bergamo with anything was made even harder.
Denis and Moralez played a one-two with each other before the former tucked past the helpless Da Costa in the 56th minute.
Atalanta were rampant and continued to press forward with Denis only denied his second of the day by a post, while Samp's poor finishing continued to prove their undoing as both Gabbiadini and Gianluca Sansone missed the target and they left Lombardy empty-handed.