Goals from Josip Stanisic, Alex Grimaldo and Jeremie Frimpong fired Xabi Alonso's side to their 17th - and most significant - win from their 21 league games this season, moving the leaders five points clear of the perennial champions in the process.
Leverkusen are still unbeaten across all competitions this season, a historic run which now stands at 31 matches, including those 21 in the Bundesliga which have seen them drop only eight points in total.
Bayern are one of the select group of clubs to have taken points off Die Werkself this term, but they were deservedly beaten in Leverkusen this afternoon as their hopes of a record-extending 12th successive title suffered the biggest blow yet.
Star striker Harry Kane was kept quiet throughout as the visitors managed just one shot on target - their lowest tally in a Bundesliga game for eight years.
Thomas Tuchel's side were found lacking in defence for the opener too, reacting inexplicably slowly to an attacking throw-in as Robert Andrich advanced down the left unchallenged and played a low ball into the box for Stanisic to convert as the statuesque visitors watched on.
The second goal arrived early in the second half when a neat passing move released Grimaldo inside the box, and the marauding wing-back fired into the roof of the net past Manuel Neuer at the near post for his eighth goal of the season.
It could have been even worse for the toothless visitors when Frimpong hit the outside of the post towards the end of normal time, but the 23-year-old full-back did get his sixth goal of the season deep into stoppage time, and in some style too.
Neuer had come up for a corner in Bayern's desperation to at least grab one goal back, leaving his goal empty, but there was still a lot for Frimpong to do as he squeezed his shot into the unguarded net from out wide on the right.
Leverkusen have famously never won the Bundesliga title before, finishing as runners-up five times, but they look increasingly likely to end that much-maligned drought following this victory.
Alonso's side are now unbeaten in their last 31 games, already a record from the start of a season for German clubs and now only one short of Bayern's all-time German record of 32 competitive matches without defeat, which they achieved under Hansi Flick from 2019 to 2020.
Leverkusen will have the chance to equal that record when they visit Heidenheim next Saturday, while Bayern must now look to regroup in time for Wednesday's Champions League last 16 first leg against Lazio.