Roberto Di Matteo's men looked set to secure a snatch-and-grab win at the Volkswagen Arena thanks to their young German midfielder, but the Belgian winger levelled the tie late on
The visitors were pegged back for most of the first half and were essentially kept in the game by shot-stopper Ralf Fahrmann, who marauded his area with great presence and continually saved Wolfsburg efforts.
On the 53-minute mark, Leroy Sane sprinted with the ball from inside his own half on a solo Schalke counterattack all the way into the opposition area to finish an excellent individual attempt.
But Wolfsburg pushed hard for an equaliser and it came late in the game when De Bruyne placed his 10th Bundesliga goal of the season effortlessly into the bottom corner from 25 yards out.
The draw leaves the hosts 12 points away from Bayern Munich at the top of the league, while Schalke leapfrogged Augsburg into fifth by virtue of goal difference.
Wolfsburg started the match in positive fashion, with De Bruyne's incisive cross looking set to allow Andre Schurrle to nip in the opener, but Fahrmann came off his line to intercept the attack.
The Belgian winger then locked his eyes on goal to loop an outrageous shot from the left flank which had Fahrmann scrambling over his line, but it dipped inches over the crossbar.
Klaas-Jan Huntelaar, who had not scored in 11 Schalke games, went down from the feeblest of touches when Naldo tackled him inside the area and the visitors' only attack of note was ended by the referee waving away his half-hearted penalty protests.
Roberto Di Matteo had Fahrmann to thank for still having a clean sheet at half-time, with the keeper pulling off a superb double-save to deny Ivan Perisic then De Bruyne from close-range with a couple of minutes left on the clock.
Wolfsburg bounced into the second half in style as Switzerland international Ricardo Rodriguez smashed the crossbar with a strike from 25 yards out.
However, it was Schalke who took the lead despite the home team's dominance as Sane picked up the ball in his own half during a Wolfsburg attack and sprinted two-thirds of the pitch into the opposition 18-yard box.
After initially getting the ball stuck between his feet, the young German regained his composure to force to ball past Diego Benaglio.
Schurrle forged a fine chance to equalise but Fahrmann's brilliance between the sticks continued as he denied the January signing a goal with yet another save.
It took 79 minutes for Fahrmann to finally be beaten, with Daniel Caligiuri's mazy run being deflected into the path of De Bruyne who did not even need a touch as he bent the ball first time into the bottom corner.
Wolfsburg threw Bas Dost on in hopes they could sneak a win they might argue their dominance deserved, but Schalke held off the intense pressure to earn a point at the Volkswagen Arena.