Bayer Leverkusen suffered their first defeat in 36 Bundesliga matches, as Leipzig came from behind to stun Xabi Alonso's side 3-2 at BayArena.
Lois Openda struck twice for Marco Rose's, who recovered from 2-0 down to make it two wins from two and move to the summit of the table.
It looked like business as usual for the reigning Bundesliga champions when they scored twice in the last seven minutes of the first half through Jeremie Frimpong and Alejandro Grimaldo.
However, Leipzig replied deep into first-half stoppage time with Kevin Kampl reducing the deficit.
Openda then brought the visitors level in the 57th minute, before a stunning long-range strike completed the turnaround 10 minutes from time, condemning Leverkusen to their first league defeat in 15 months.
Data Debrief: Leverkusen's long streak comes to a shuddering halt
Leipzig became the first side to beat Leverkusen in a Bundesliga match since Bochum achieved the feat a staggering 462 days earlier.
The visitors have begun a Bundesliga season with two wins from two for only the second time, also doing so in 2019-20.
They are also now unbeaten in 13 league matches, their longest such streak since Rose took charge.
As for Leverkusen, their invincible streak is officially history, as is their 29-game unbeaten run on home soil.