Stefan Kiessling put the visitors in front in the third minute, but the Wolves turned the game around rather fortunately with goals from Patrick Helmes and Ashkan Dejagah giving them the lead at half-time against the run of play.
Michal Kadlec gifted them a third with an own goal after an hour before Eren Derdiyok pulled one back for Leverkusen in stoppage time.
Leverkusen needed just three minutes to put their midweek Champions League nightmare behind them and go in front at the VW-Arena.
Andre Schurrle broke into the penalty area and then squared the ball to give Kiessling a simple tap-in from close range.
Kiessling almost made it two just minutes later, but his shot from a tight angle was blocked by Marcel Schafer.
Gonzalo Castro's shot was also blocked as Leverkusen threatened to deliver the same kind of mauling that they had suffered on Wednesday, but their failure to score goals with the same ease as Barcelona cost them as the Wolves fought their way back into the game.
They levelled in the 32nd minute with Helmes scoring his second goal in three games, heading in Makoto Hasebe's cross from the right at the far post.
Dejagah then gave the Wolves a scarcely deserved lead on the stroke of half-time. Mario Mandzukic headed the ball into the path of Dejagah, who left Bernd Leno no chance with his powerful drive from a tight angle.
It was clearly not Bayer's day once again as they fell 3-1 down in the 61st minute, with Kadlec scoring an own goal as he attempted to clear Dejagah's cross.
Bayer did not capitulate as they had done in Spain, though, and they kept the game alive with Kiessling testing Diego Benaglio with a header before Derdiyok earned them a consolation in stoppage time.
The Switzerland striker headed in Castro's free-kick before Karim Bellarabi almost grabbed a dramatic equaliser with the last kick of the game, sending his shot just inches wide of the post as Wolfsburg just managed to hold on to all three points.