A dominant Belgium saw off Scotland 3-0 in Brussels with Romelu Lukaku on the scoresheet twice.
The Manchester United striker found the net either side of half-time as Scotland, without the injured Andy Robertson, wilted under the pressure.
De Bruyne hammered in a third in stoppage-time to send the boisterous home support away satisfied, with Scotland struggling to threaten until late.
Scotland also lost Stuart Armstrong to a first-half injury, on an expectedly difficult evening for Clarke’s side.
Robertson’s absence meant a debut for Greg Taylor, as Clarke made the bold move of replacing five players from the win over Cyprus. James Forrest, Ryan Fraser and Eamonn Brophy – Saturday’s front three – were all benched, as Johnny Russell, Stuart Armstrong and Oliver Burke all started. Scott McTominay took McGinn’s place in midfield.
Belgium had not lost a competitive game at the King Baudouin since September 2010 and against Scotland, their only defeat in the last 47 years came in a European Championship qualifier at Hampden Park in 1987.
The odds were stacked against the travelling side in their bid to keep their Euro 2020 campaign on some sort of track.
Scott McKenna, again starting alongside Charlie Mulgrew at the back, had plenty of early defensive work to do in getting in the way of a Lukaku effort.
Burke netted the winner against Cyprus and started promisingly, gather Armstrong’s flick and sliding an effort across the face of goal.
David Marshall would have expected to be busy before kick-off and Belgium did not disappoint him. A wonderful weaving run from Hazard, forcing Mulgrew to back track, created space for Kevin De Bruyne to shoot and the Hull City stopper reacted well to tip it over.
He looked a little shakier from the resulting corner, with Axel Witsel’s strike spilled in close proximity to Lukaku before Marshall could gather. De Bruyne again looked to be in the right place at the right time when Russell sold Taylor short but he lashed wide.
Scotland were gradually dragged deeper towards their own goal and offered no real threat to Belgium on the counter. Lukaku managed to backheel against his standing leg six yards, which frustrated the provider, but would make amends before the break.
McTominay looked to have seen off the danger by nipping the ball off Hazard but the Real Madrid-bound forward kept going and regained the ball. His cross to the back post was weighted perfectly for Lukaku, who guided his header in.
Belgium began the second period with the intent to kill the game off, with Lukaku heading wide when left unmarked and Marshall required to beat away a De Bruyne free-kick.
Lukaku grabbed his second on 57 minutes with more clever marksmanship. Hazard and De Bruyne again had a role to play, with the former feeding the Man City midfielder to test Marshall from the edge of the box. His parry landed straight at the feet of Lukaku, who finished first-time.
The home side were in cruise control and Lukaku twice dragged wide a hat-trick chance, while the outstanding Hazard curled another chance past the post.
Scotland had to wait until the 80th minute to force a meaningful save out of Thibaut Courtois, with Ryan Fraser teasing a strong right hand out of the giant goalkeeper.
De Bruyne capped off a masterful display with a late third, ensuring Belgium continued their 100 per cent start to qualifying.
