In the 10th minute, Lookman seized the opportunity after Marten de Roon's header landed in his path. The London-born Nigerian international swiftly struck the ball past Napoli's goalkeeper Alex Meret from a short distance.
He doubled Atalanta's lead with a superb curling shot just after the half-hour mark. Napoli coach Antonio Conte was furious that his defence gave Lookman the space to shoot.
The home side created few chances. Former Manchester United midfielder Scott McTominay hit the post with the best of them.
Mateo Retegui added a third goal for Atalanta in injury time, his 11th of the season, and the visitors were able to celebrate as they moved onto 22 points, just three behind Napoli.
"We had a great match, bringing three points back from the league leaders is a great source of pride," Lookman told DAZN.
Atalanta coach Gian Piero Gasperini added: "When you come to play in Napoli against a team that has had a great start to the season, you know that you have to have a great match. We are very satisfied."
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"We are a team that is growing, making progress. We have made eleven changes to the squad compared to the one that played in the middle of the week, but we still need to improve things."
'Don't be ashamed'
Conte shrugged off the setback.
"We shouldn't be ashamed of this defeat, they have been playing together for a long time, they are better structured than us," he said.
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Inter edged out Venezia 1-0 thanks to a 65th-minute goal from skipper Lautaro Martinez who scored from a cross by Federico Dimarco.
Venezia thought they had grabbed a stoppage time equaliser but Marin Sverko's effort was ruled out by VAR for a foul by the Croatian defender.
"We clearly need to be more clinical, we shouldn't find ourselves in such a situation given the number of chances we had," said Inter coach Simone Inzaghi.
"This is going to be a very open championship, with several teams who can aim for the title. This kind of victory can make the difference."
Champions Inter and Napoli clash at the San Siro next Sunday.
Fiorentina joined Atalanta on 22 points after Moise Kean struck in the 41st minute to give his side a 1-0 win at Torino.
Roma slipped to a 3-2 loss at the hands of Verona, a third defeat in four matches.
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They are 11th with 13 points with more pressure building on coach Ivan Juric who only took over in September to replace Daniele De Rossi
(This story has not been edited by staff and is auto-generated from a syndicated feed.)