Before kick-off, Wales knew that three consecutive victories would secure their spot at a second successive WC.
Motivated by that objective and buoyed by a spine-tingling rendition of the national anthem, Wales made an electric start to proceedings and deservedly took the lead through Joe Rodon in the eighth minute.
The Leeds United defender got away from his marker to tower high and head home from Sorba Thomas’ deep corner.
Unfortunately for the hosts, the momentum built by Rodon’s second international goal was soon quashed by a disastrous six-minute spell.
Belgium's De Bruyne calmly levelled the scoreline from the penalty spot after Ethan Ampadu had been penalised for a handball upon review.
Thomas Meunier then completely took the wind out of Wales’ sails when he latched onto Jérémy Doku’s cut-back to lash a fierce strike past Karl Darlow, stunning the home faithful into an eerie silence.
Those supporters were at least given a sign of encouragement when Jordan James forced Thibaut Courtois into a diving stop in the closing stages of a gripping first half in the Welsh capital.
Craig Bellamy’s enjoyed large periods of possession after the restart and showed plenty of promise despite seeing Doku threaten with a curling effort past the far post.
However, with Belgium standing firm, the Wales boss introduced Brennan Johnson and then Nathan Broadhead for the injured Davies in the hope that the attacking duo would inspire a turnaround.
But those hopes were dealt a major blow when James’ careless handball allowed De Bruyne to slot home from the spot for the second time in the contest.
Broadhead still managed to leave his mark on the game, drilling a clinical strike past Courtois at the near-post, but Leandro Trossard made sure that effort counted for very little, as he quickly restored Belgium’s two-goal cushion with a composed 90th-minute finish.
A fourth consecutive H2H defeat leaves the Dragons four points adrift of top spot and a point away from North Macedonia in second.
Flashscore Man of the Match: Kevin De Bruyne (Belgium)