Bayern Munich suffered their first defeat since December 2019 as they were well beaten at Hoffenheim.
Bayern had won their past 23 matches, and were unbeaten in 32, a run that saw them win last season's treble and the Uefa Super Cup on Thursday.
Ermin Bicakcic headed the hosts and Munas Dabbur doubled their lead, before Joshua Kimmich's fine goal for Bayern.
But Andrej Kramaric scored twice, including an injury-time penalty, to seal a famous Hoffenheim win.
The hosts are managed by Sebastian Hoeness, who was Bayern's youth coach last season.
Champions Bayern, who brought on Robert Lewandowski in the second half after starting him on the bench, had beaten Schalke 8-0 in their opening Bundesliga game.
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