Bundesliga Review: Hoffenheim enjoy big win, Freiburg falter late on
The visitors were in front after 23 minutes thanks to an own goal by John Brooks and the defender's day went from bad to worse when he conceded a penalty soon after for bringing down Sven Schipplock.
Sejad Salihovic converted that spot-kick and netted another in the 39th minute after Andreas Beck was fouled by Nico Schulz in the area.
Schipplock added a fourth from close range in the 75th minute and Sebastian Rudy completed the rout late on in front of a stunned Olympiastadion crowd.
Bottom club Freiburg suffered late heartbreak as they surrendered a 2-0 lead to draw 2-2 with Hannover on home turf.
Mike Frantz opened the scoring in first-half stoppage time and Freiburg looked on course for their third league win of the season when Marc-Oliver Kempf doubled the advantage nine minutes from the end.
However, Leonardo Bittencourt pulled one back almost immediately and Joselu's 93rd-minute strike earned a point for Hannover.