Having made last year’s final, Atletico were big favourites against the out-of-form Leverkusen, but they lost 1-0 in the first leg of their last-16 match thanks to a stunning strike from Hakan Calhanoglu.
Diego Simeone’s team were outplayed by the Germans for the majority of the game and ended with 10 men after Tiago was sent off for a second bookable offence.
The experienced midfielder will miss the second leg in the Spanish capital and Simeone will also be without key defender Diego Godin, who was shown his second yellow card of the knockout stages in the second half.
Leverkusen, who had won just one of their previous five matches, looked anything but underdogs in the opening exchanges as they set about shocking the visitors with an early goal.
They almost got one in the 12th minute when Emir Spahic’s shot trickled through a crowded penalty box, but luckily for Mario Mandzukic was there to hook the ball clear off the line.
Spahic came even closer to scoring soon after when he let fly with a 30-yard shot which beat the diving Miguel Moya but cracked the woodwork.
Atletico were struggling to get into the game and Simeone made two substitutions.
Guilherme Siqueira, who had taken a kick to his ankle earlier in the match, was replaced by Jesus Gamez and the ineffective Saul Niguez came off for Raul Garcia.
With Juanfran pushed further up the field, Atletico looked more dangerous and they ended the first half strongly.
Arda Turan looped the ball up over Bernd Leno towards but the goalkeeper recovered just in time to claw the ball away from Antoine Griezmann, who was ready to tap in.
The Leverkusen stopper then pulled off the save of the night to deny Tiago from 12 yards.
Leverkusen started the second half exactly as they did the first – by pressing the visitors – but this time, they got their reward in the form of a goal.
And what a goal it was. Karim Bellarabi drifted from the left flank to the right, taking three Atletico players with him. He held them off, then backheeled the ball into Calhanoglu’s path and he drilled a fierce rising shot past Moya at his near post.
Simeone’s night worsened when Godin scraped his studs along Lars Bender’s knee to earn the booking that will keep him out of the second leg.
The Atletico coach turned to Fernando Torres for inspiration. The former Chelsea striker replaced Turan with 25 minutes left.
Torres almost made an immediate impact, but Reno blocked the striker’s shot from close range.
The striker had the ball in the net moments later when he headed in from a corner, but the referee ruled the ball had gone out of play before Torres bundled home.
Leverkusen – despite their best efforts – could not find a second, but they will be happy to take a one-goal advantage to the Vicente Calderon for the return leg in three weeks’ time.