With Roberto Martinez's side trailing to an early Yussuf Poulsen goal, De Bruyne came off the bench for the second half, his first outing since injury forced him off during Manchester City's Champions League final defeat to Chelsea.
And the 29-year-old quickly provided a brilliant assist for Thorgan Hazard before turning the game completely on its head with an equally superb finish that secured the points.
Just five days on from those traumatic scenes involving Christian Eriksen in Copenhagen, the home fans welcomed their heroes back to Parken by creating an electric atmosphere.
The consequences of that were apparent just two minutes in as Jason Denayer played a panicky pass out from the back that was easily intercepted by Pierre-Emile Hojbjerg.
The Tottenham midfielder did well to shrug off his man in charging toward goal and poke the ball to Poulsen, who produced a powerful low finish into the bottom corner from just inside the box.
That early strike served to further stir the Danes, who twice went close moments later as Joakim Maehle saw a shot smothered and Martin Braithwaite flicked goalward from a low cross.
Proceedings were paused after 10 minutes for a short period of applause in support of the absent Eriksen, a tribute that served to somewhat dull the hosts' momentum.
But Belgium was relieved to see a Mikkel Damsgaard effort dribble wide of the post after great footwork in the box, once Denmark got going again after the half-hour mark.
The visitor's poor performance prompted a half-time change, the ineffective Dries Mertens making way for De Bruyne.
And the substitute made an almost immediate impact, building on a trademark burst forward from Romelu Lukaku by sitting down two opponents before teeing up Thorgan Hazard to level up from close range.
De Bruyne then went one better, getting on the end of a slick team move to smash a low, left-footed drive home from the edge of the penalty area, in front of the delighted Belgian supporters.
Denmark made a late push to get back on terms, going closest when Braithwaite brushed the bar with a header at the death, but they were ultimately held at arm's length by a team who strengthened its credentials as a potential tournament winner.