Patrick Herrmann played a key role at Borussia-Park, with two goals and an assist, as Lucien Favre's side completed a 17th game without defeat in all competitions.
It was Herrmann who provided the cross for Andre Hahn to open the scoring in the 12th minute.
Anthony Modeste finished off a neat move to draw Hoffenheim level on the half-hour, but the hosts reclaimed the lead within two minutes as Herrmann flicked a Hahn cross over Oliver Baumann.
Herrmann then doubled his tally seven minutes after half-time with an opportunistic finish.
Havard Nordtveit had a low free-kick saved by Baumann, but the loose ball dropped to Herrmann, who made no mistake from 10 yards.
Freiburg lifted themselves off the bottom of the table with a 1-0 victory over Cologne, their first win of the campaign.
Vladimir Darida's 50th-minute penalty proved decisive at the RheinEnergie Stadion, lifting Christian Streich's side above Werder Bremen and Borussia Dortmund into 16th.
Paderborn, meanwhile, moved into seventh place with a 3-1 win over Hertha Berlin at the Benteler-Arena.
Salomon Kalou grabbed his fourth goal of the season after 41 minutes to cancel out Marvin Bakalorz's opener.
However, Paderborn were not to be denied and pulled clear in the second half through a header from Elias Kachunga and Alban Meha's powerful strike from the edge of the penalty area.
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