Fiorentina fully deserved their opener on 15 minutes after starting off the stronger side, with Roberto Mandragora recycling a corner via a teasing cross which was met by Robin Gosens and saved brilliantly by Marco Carnesecchi, but Lucas Martinez Quarta followed in on the rebound.
That kicked off a free-scoring first half which saw the lead swing back and forth between the two sides.
There was little the Viola could do to stop a sensational equaliser as Lookman sublimely took it past Edoardo Bove and crossed in to Mateo Retegui, who nodded down past David de Gea for his fourth strike in as many matches for La Dea.
However, the visitors soon regained their advantage through the in-form Moise Kean, who tapped in at the far post from a Gosens header for his second Serie A strike of the season.
Having failed to score a league goal at all in the previous campaign, the former Juventus man was made to rue hitting the post with his next chance though, as Atalanta sensationally turned the match on its head on the stroke of half-time.
Ederson whipped in a dangerous ball, allowing a towering Charles De Ketelaere to bury his header from close range. Just one minute later, a stunned Fiorentina defence let Lookman speed away on the left, and the Europa League final hero cut in to roll inside De Gea’s near post.
There was a more muted feel to the restart, but what few chances presented themselves were for the hosts to extend their lead. Somehow Raoul Bellanova failed to nudge past the goalkeeper following a defensive mix-up, before Lookman sliced wide after some fluid link-up play with Retegui.
Their dominance continued, and if it wasn’t for a variety of saves from De Gea to deny each of De Ketelaere, Davide Zappacosta and Lookman, the Nerazzurri would have been well out of sight.
Lookman then skied a clear chance as he looked to cap off what had been a stellar display, but that wasn’t pivotal in the end as Fiorentina never got their attack going beyond the break and failed to to salvage a point.
Getting revenge for a 3-2 loss in this fixture at the end of the last campaign, Atalanta got their start to the season back on track after two consecutive defeats, while the visitors saw a seven-match unbeaten league run come to an end having led twice.
Flashscore Man of the Match: Ademola Lookman (Atalanta)