Khvicha Kvaratskhelia and Amir Rrahmani scored in the second half for Napoli to go 18 points clear of second-placed Inter Milan on Saturday.
Lazio could leapfrog Inter with a win at Bologna late.
Atalanta's fifth loss in seven matches diminished further their chances of qualifying for the Champions League. Atalanta were placed sixth, five points below fourth-placed Roma ahead of the Giallorossi's match against Sassuolo on Sunday.
Napoli were looking to bounce back from losing to Lazio last weekend, their second league loss.
They play Eintracht Frankfurt in the Champions League last 16 on Wednesday, leading 2-0 from the first leg, but coach Luciano Spalletti opted not to rotate his squad.
Napoli dominated and almost broke the deadlock in spectacular fashion at the start of the second half but Victor Osimhen's overhead kick was straight at Atalanta goalkeeper Juan Musso.
Instead, Kvaratskhelia scored an impressive opener on the hour mark when he collected the ball from Osimhen and weaved his way into the area, twisting and turning between defenders, before blasting into the roof of the net.
Rrahmani all but sealed the win in the 77th when he headed a corner into the far bottom corner.
Udinese got back to winning ways by 1-0 over Empoli.
Rodrigo Becão headed in early in the second half to help Udinese to their first win since January.
Udinese moved level with Bologna and Juventus, seven points below Atalanta. Empoli remained 10 points above the relegation zone.
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