Wolfsburg crowned an excellent first-half display with the opening goal through Ivica Olic.
At that stage the Wolves were sitting in fourth place and on course for a place in the Champions League next season, but they were unable to hold onto their advantage for long as Robert Lewandowski and Marco Reus turned the tables in a much-improved second half for the Westphalians.
Dortmund came into the game - their first of two against Wolfsburg, who they meet again in the DFB-Pokal semi-final - reeling after a 3-0 defeat to Madrid left their hopes of reaching the semi-finals of the Champions League in tatters.
Their pride also seemed wounded as they struggled - not for the first time this season - to get their usual flowing attacking football going.
Wolfsburg took a bit of time to realise that they had the chance of picking up maximum points, but as Dortmund's meandering persisted Dieter Hecking's men started to raise their game.
Olic went close with the first chance of the game, just missing the target at full stretch before Kevin De Bruyne wasted another opportunity.
The visitors were starting to get on top when they took a deserved lead 10 minutes before the break.
Former Dortmund player Ivan Perisic pulled the ball back for Ricardo Rodriguez to deliver a cross from the left to the far post, where Junio Malanda got in a header.
Mitchell Langerak, standing in for the injured Robert Weidenfeller in goal, managed to keep the ball out, but he gifted the ball to Olic, who scored from close range.
Dortmund coach Jurgen Klopp rung the changes at half-time with Milos Jojic and Erik Durm coming on for Nuri Sahin and Pierre-Emerick Aubameyang.
The two substitutes brought more threat to the Dortmund attack and after Durm's cross resulted in a corner, they levelled. Reus curled the ball in from the corner and Lewandowski rose to head past Wolfsburg goalkeeper Max Grun.
Dortmund were now well on top and they created several chances before taking the lead in the 77th minute.
Durm's cross was plucked out of the air by Grun, but he clashed with team-mate Robert Knoche and the ball squirmed free to Reus, who accepted the gift.
Dortmund had chances to make the win a more convincing one but a third goal was not required as they opened up a three-point advantage over third-placed Schalke, and 10 points over Borussia Monchengladbach in fourth, to practically secure their berth in the Champions League again next season.