Atalanta were looking to lay down a marker to leaders Napoli, and they wasted no time in making their intentions clear.
After Marco Carnesecchi brilliantly denied Christian Pulisic early on, Charles De Ketelaere broke the deadlock.
The ex-Rossoneri forward rose high above Theo Hernandez to head in Marten De Roon’s lofted free-kick, marking Atalanta’s league-best seventh goal inside the opening 15 minutes this term.
However, Gian Piero Gasperini - serving the second of his two-match touchline ban - could only watch as his side’s lead evaporated just 10 minutes later.
Rafael Leao whipped in a perfect cross from the left flank, allowing Alvaro Morata to slide in and restore parity.
La Dea had chances to re-establish their advantage before half-time, but Paulo Fonseca’s men were spared by their hosts’ wastefulness in front of goal.
To add to the Rossoneri’s frustration, Pulisic was forced off injured before the break, weakening their forward line heading into the second half.
Both sides pushed to seize control in an increasingly end-to-end contest following the restart. Milan carved out the first chance through Tijjani Reijnders, while Raoul Bellanova squandered a golden opportunity at the other end at the far post as the hour mark approached.
With no shots on target, and just five attempts from both sides combined since the break, the Gewiss Stadium was set up for a tense final quarter-hour.
Lookman forced Maignan into a superb save after picking up Lazar Samardzic’s pass 10 minutes from full-time, but the Nigerian wasn’t to be denied again three minutes from time as he headed home at the far post to seal victory for La Dea, who have now won nine successive matches across all competitions.
Meanwhile, Milan suffer a first defeat since falling to Napoli almost two months ago, with Fonseca’s men now falling out of the Serie A top-six and the European spots with the defeat.