Just a day after being drawn against Barcelona in the last 16 of the continental competition, Leverkusen suffering an embarrassing home loss as Daniel Didavi gave Nuremberg the lead after eight minutes and Jens Hegeler made it 2-0 inside the first quarter of the game.
Tomas Pekhart killed the game off with his goal in the 73rd minute to end Leverkusen's six-game undefeated run and lift his side three points above Kaiserslautern, who host Hannover tomorrow.
Nuremberg took the lead in the eighth minute as Christian Eigler's diagonal cross found Didavi, who out-paced Sidney Sam and then fired across Leverkusen keeper Bernd Leno and inside the far post.
The visitors remained the better side and doubled their advantage after 22 minutes from a set-piece, with Hegeler meeting Marvin Plattenhardt's corner nine yards out and finding the bottom right corner.
Nuremberg keeper Raphael Schafer kept his team two goals ahead with two superb saves in the 33rd minute, stopping Eren Derdiyok's shot from 14 yards and Michael Ballack's follow-up header.
Nuremberg were close to extending the lead after 54 minutes as Leno blocked Pekhart's shot and the Czech striker's second attempt was saved by Daniel Schwaab.
But they got their third goal in the 73rd minute, with Pekhart heading in Plattenhardt's corner from six yards.