De Bruyne opened the scoring and set up the second goal for Michy Batshuayi at the King Baudouin Stadium, as the Red Devils remained three points behind leaders Netherlands in Group A4.
Kieffer Moore pulled one back for Wales, but the Dragons must now beat Poland on Sunday to have any chance of avoiding relegation from League A.
The Red Devils, whose head coach Roberto Martinez was sent from the touchline for time-wasting, need an emphatic win over the Dutch when they meet on Monday to reach the Finals.
Belgium took just 10 minutes to break through as De Bruyne applied a wonderful first-time finish to Batshuayi's lay-off to the edge of the penalty area.
Youri Tielemans steered Yannick Carrasco's cross off target and Batshuayi fired over from a tight angle as the Red Devils continued to dominate, while the woodwork denied De Bruyne a second goal as he rattled the post from 20 yards out.
Eden Hazard then curled narrowly wide before the host doubled its lead in the 37th minute. This time, De Bruyne was the provider; sweeping in a pinpoint cross for Batshuayi to touch home.
Ethan Ampadu called Thibaut Courtois into action with Wales' first attempt on goal, while Wayne Hennessey denied De Bruyne at the other end.
The visitor halved the deficit within five minutes of the restart as Moore rose to head home Brennan Johnson's inviting cross.
Rob Page introduced Gareth Bale in the 64th minute and the Los Angeles FC forward went close soon after, Toby Alderweireld deflecting his header over from Dan James' centre.
VAR overturned a Belgian penalty later on, but the hosts held on for maximum points after Martinez was ordered from the touchline in stoppage time.