Sidney Sam's decider inflicted front runner Bayern Munich the first loss of the season to stop their perfect start meanwhile Vedad Ibisevic ensured Stuttgart's first win on home soil and Monchengladbach came from behind to win 3-2 at Hannover, to close the ninth round of Bundesliga on Sunday.
Record champions Bayern Munich dropped points as Leverkusen secured a historic 2-1 away win since 1989.
After the kick-off the Bavarians took over the reins whereas Leverkusen defended deep to lurk for counter attacks. Nevertheless the hosts lacked in precision as Mario Mandzukic, Phillip Lahm, Thomas Mueller and Toni Kroos pulled just wide.
Leverkusen's Stefan Kiessling found the back of the net at the 28th minute but the referee declared the goal invalid owing to a foregone foul play.
However, three minutes before the break, Leverkusen caught Bayern flat footed when Kiessling finished a counter, following a diagonal pass by Andre Schuerrle, to open the scoring against the run of the game.
After the interval Bayern started a run on Leverkusen's goal but all their efforts remained fruitless until the 77th minute when Mario Mandzukic nodded home a Claudio Pizzaro cross to level the score.
The Bavarian's tried to take advantage of their momentum to besiege Leverkusen's goals but for all that Mandzukic?s deflected effort only rattled the right post.
The "Werkself" flabbergasted the record champion with four minutes left as Sidney Sam's header found the back of the net, thanks to a curious deflection by Bayern defender Jerome Boateng.
"The loss won't throw us off track but we have to draw lessons from it," Bayern coach Juppy Heynckes said.
Bayern stay on top of the standings with a four-point cushion whilst Leverkusen remains on fifth position.
Elsewhere, Stuttgart overpowered Frankfurt 2-1 to wrap up the first win on home soil. Vedad Ibisevic headed the winner with six minutes left to inflict newly promoted stunner Frankfurt the second loss.
Monchengladbach needed nine minutes at Hannover to turn a 2-0 deficit into a 3-2 victory. Its Hannover's first defeat in 23 matches on home soil.
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