A fervent pre-match atmosphere in the Spanish capital was quickly calmed by the visitors, who displayed great authority over possession in the early stages.
Whistles were soon spreading around the Metropolitano crowd as Die Werkself continued to dominate, with Florian Wirtz and Nathan Tella both denied by Jan Oblak, while Tella also had a strike ruled out for an offside in the build-up.
Atleti’s task of growing into the game was made all the more difficult on the 25-minute mark, however, as after initially being awarded a yellow card, Pablo Barrios was sent off after a VAR review for a high challenge on Nordi Mukiele.
Diego Simeone’s men needed to rely on all of their famed defensive mastery to weather the Leverkusen storm, and they were certainly effective as the visitors seemed to run out of ideas as the interval approached.
In fact, Atleti rallied and were offering more threat than when they had a full complement at their disposal.
However, in the first minute of stoppage time, Xabi Alonso’s men delivered a sucker punch as Piero Hincapie headed home at the back post from Mukiele’s cross to send Leverkusen in at the break with a lead.
Alonso looked to press home his side’s advantage by replacing wing-back Mukiele with striker Patrik Schick for the second half. However, his changes had the opposite effect, as just seven minutes after the restart the hosts levelled the contest out of nowhere.
A counter-attack at lightning speed saw Antoine Griezmann play a long ball in behind, and Julián Alvarez pounced to beat a labouring Jonathan Tah to it, held off Alejandro Grimaldo, and scuffed a shot into the bottom corner past Matěj Kovář.
Atlético were suddenly on top, and after a lull in the contest, Leverkusen’s numerical advantage was eliminated when Hincapié received a second yellow card for a clumsy foul on Giuliano Simeone.
Die Werkself had completely lost their control of the contest, with the vociferous home support thriving in the chaos ensuing on the pitch, spearheaded by Simeone - both senior and junior.
With Leverkusen rattled, there was a sense of inevitability about the direction of the winning goal, and indeed the scorer, as Alvarez was found by Angel Correa and rounded Kovář before slotting in a goal that extends his side unbeaten run in home H2Hs to six matches.
Leverkusen, meanwhile, suffer just a fourth defeat since the start of last season as their poor record in Spain continues – last winning a European away on these shores in 2013/14.