The Brazilian defender punished struggling Dortmund for poor marking when he rose unchallenged to head home an inswinging corner with a towering header.
Ciro Immobile's stunning strike had looked to have given Jurgen Klopp's side victory at Signal Iduna Park, but they were unable to see Wednesday's game out.
The hosts were given an early warning when De Bruyne was denied by goalkeeper Mitchell Langerak after exchanging passes with Vieirinha and the Belgium midfielder fired the rebound off target.
Immobile had a golden opportunity to restore Dortmund's advantage when Sebastian Kehl, passed fit after recovering from a rib injury, fed him with a lovely ball over the top, but Diego Benaglio surged off his line to keep out the Italy international's volley.
Wolfsburg then came close just three minutes into the second half when Ivan Perisic was unselfish as he laid the ball off for the unmarked Vieirinha in the area, but Langerak narrowed the angle and made a fine save.
Dortmund continued to cause problems for the Wolfsburg defence and it took a fine save from Benaglio to keep out a strike from Immobile which looked destined for the back of the net, with Hummels' goalbound effort from the resulting corner blocked.
Wolfsburg lost Vieirinha to what appeared to be an ankle injury before Immobile came close once again when Aubameyang headed the ball down to him and he surged forward before unleashing a rasping drive which was just off target.
Immobile finally found a way through when he surged forward and beat Benaglio with a fine finish from around 20 yards out 14 minutes from time.
But there was a final twist as Naldo was left unmarked by Kehl and headed home a Ricardo Rodriguez corner to deny the hosts and keep them in the drop zone.
