With the Red Devils 2-0 up, De Bruyne laid on goals for Eden Hazard and Romelu Lukaku to put his side firmly in control.
Georgiy Dzhikiya pulled one back for the hosts late on but Belgium were comfortable winners.
The result sees Belgium continue their perfect Group I record, with Roberto Martinez’s side now six points clear of second-place Russia with a game remaining.
Belgium play their final qualifying match when they welcome Cyprus to Brussels on Tuesday.
Meanwhile, Ilkay Gundogan played the full 90 minutes as Germany defeated Belarus in Group C.
The midfielder assisted Toni Kroos' 83rd-minute strike that capped an emphatic victory.
The result leaves the Germans top of Group C with a game remaining, two points ahead of Holland.