A recent dip in form saw Atalanta recently draw three Serie A games in a row and drop to third place after leading at Christmas, but the visit of Napoli gave them the chance to close the gap on the leaders.
They looked well positioned to do just that as the division's top scorer, Mateo Retegui, scored his fourteenth goal of the season thanks to a fantastic strike from an angle into the roof of the net.
In response, David Neres had a shot saved before the visitors leveled the score shortly before the half-hour mark.
From a similar position, Matteo Politano hammered a fierce goal past Marco Carnesecchi, leaving the goalkeeper without a chance.
With momentum on their side, Antonio Conte's men were soon ahead thanks to another clinical finish, this time from Scott McTominay, who put aside Andre-Frank Zambo Anguissa's cutback into the top corner from just inside the penalty area.
A quiet start to the second period followed until Atalanta's talisman Lookman provided a moment of quality.
Politano seemed to have avoided any danger, but the Nigeria international adapted and buried himself in the corner to restore parity.
La Dea then came close to taking the lead, with only a fingertip save from Alex Meret preventing Charles de Ketelaere's header from nestling into the bottom corner.
Atalanta looked all the more likely to find a winner, but the next goal came at the other end when Romelu Lukaku, otherwise calm, headed Anguissa's sharp cross into the corner.
In true Conte fashion, his side ran out the clock with confidence to triumph and move six points clear at the top.
Inter Milan still have two games remaining to overtake them, but their 2-2 draw with Bologna in midweek suggests taking six points from six is no guarantee.
Atalanta are now seven points behind the Partenopei and will need to break their current five-match winning streak quickly if they want to stay in contention for a first Serie A title.
Flashscore Man of the Match: Andre-Frank Zambo Anguissa (Napoli)
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