Looking to take the chance to move into the top three, the home side started brightly and found the breakthrough after just nine minutes.
Wouter Burger lined up a free-kick in a wide position, and despite the angle favouring a cross, he whipped a perfect effort over Mark Flekken and into the far top corner.
A chance for a second came shortly afterwards, thanks to a swift break from the back, but Fisnik Asllani could only hit his effort directly at Flekken.
The visitors shaded the overall possession stats throughout the half but lacked impetus in the final third, as Hoffenheim continually posed a threat on the counter-attack.
Leverkusen finally created a chance as the interval approached when Patrik Schick improvised a backheel towards goal at the far post, but it lacked the necessary power to trouble Oliver Baumann.
The visitors responded with a double substitution at half-time, but it had little impact on the game's momentum, as Die Kraichgauer remained the more dangerous side.
Burger came close to adding his second of the game shortly after the restart, but Flekken did just enough to awkwardly push his shot into the air before it spun behind for a corner.
Kasper Hjulmand’s men finally had a golden chance to equalise on 68 minutes when Alejandro Grimaldo’s free-kick forced an inspired save from Baumann, before Schick volleyed the rebound over from close range.
Hoffenheim ultimately managed to shut Leverkusen out for most of the closing stages, securing a vital victory in their top-four chase of a direct rival. A second successive defeat is Leverkusen’s fourth loss in six Bundesliga trips, and leaves them four points adrift of Hoffenheim.
Flashscore Man of the Match: Wouter Burger (Hoffenheim)
