Three goals in 14 first-half minutes provided Markus Gisdol's men with a comfortable advantage in Gelsenkirchen.
Kai Herdling put Hoffenheim ahead in the 21st minute before Roberto Firmino took centre stage, laying on a goal for Kevin Volland and then finding the net himself.
Dortmund's second goal arrived four minutes into the second half through Jonas Hofman.
Elsewhere, an 84th-minute strike from Ivo Ilicevic spared Hamburg's blushes in a 2-1 win over Cologne.
Adam Matuszczyk cancelled out Maximilian Beister's impressive opener for Hamburg, but the Imtech Arena hosts were still able to claim victory thanks to Ilicevic's late intervention.
Willi Orban, Simon Zoller and Marcel Gaus were on target for the side lying third in Germany's second tier.
