The first game back after Germany's mid-season break gave Wolfsburg's players and fans the opportunity to honour the life of 20-year-old midfielder Junior Mandala, who died in a car crash earlier this month, before kick-off.
Dieter Hecking's team, who were 11 points behind leaders Bayern in second before Friday's match, proceeded to give a stirring performance from the first whistle - Bas Dost handing them a fourth minute lead.
Although Juan Bernat hit back for Bayern two minutes later, De Bruyne would mesmerizingly turn Dante inside-out to rifle in an unstoppable fourth and seal Bayern's worst league defeat since a 5-1 thrashing on the same ground in April 2009.
Following a poignant pre-match tribute to Mandala - commemorated with a lengthy period of applause before a moment's silence - Wolfsburg stylishly took the lead from their first attack.
Luiz Gustavo intercepted Thomas Muller's pass to launch a clinical counter-attack. Daniel Caligiuri’s exquisite throughball from the right picked out De Bruyne, who selflessly touched the ball into Dost's path to stroke home.
The champions' usual poise deserted them as the half wore on and they might have been further behind when Xabi Alonso carelessly gave away possession to De Bruyne, but he was unable to pick out Dost on this occasion – the Dutchman scuffing another effort wide soon after.
Bayern half-cleared a stoppage-time set-piece and, although Dost's contact did not appear to be completely clean, the Dutchman lashed into the top corner via the upright.
Though Caligiuri could not convert Ivan Perisic's superb left wing cross soon after the interval, Wolfsburg once again would not pay for their profligacy as Bayern's defensive efforts completely unravelled.
Centre-halves Jerome Boateng and Dante's eagerness to press up the field was exposed as a simple pass from Maximilian Arnold sent De Bruyne racing clear to finish coolly.
