It was a frustrating first half for Roberto Martinez’s men but a superb strike by Dries Mertens broke the deadlock at the start of the second period before two Romelu Lukaku goals gave Belgium some breathing space.
Eden Hazard was in the Belgium team despite hobbling off against Costa Rica in a friendly prior to the tournament, but Martinez’s men were without central defenders Vincent Kompany and Thomas Vermaelen, so Celtic’s Dedryck Boyata started for what was his eighth cap. Panama captain and national hero Roman Torres, whose late goal secured qualification for their first World Cup, recovered from a hamstring injury to take his place in the side.
Belgium were quick out of the blocks and it looked ominous early on for Panama. Lukaku clipped an effort over the crossbar before Yannick Carrasco and then Mertens worked goalkeeper Jaime Penedo.
There was a heart-stopping moment for Torres after 12 minutes when his pass to Penedo was seized upon by Hazard, but he could only send his shot into the side-netting from a tight angle.
A quickly-taken corner almost caught Panama napping after 20 minutes but Mertens steered his effort narrowly wide.
A superb last-ditch sliding challenge by Torres prevented a simple tap-in for Lukaku shortly afterwards and it seemed only a matter of time before Belgium made the breakthrough. However, Panama continued to frustrate their highly-rated opponents and it was not until half-time approached that Belgium managed to really threaten again.
Penedo pushed away a shot from Hazard following a driving run from the Chelsea midfielder and then raced out quickly at the feet of Lukaku when it looked like the Manchester United striker was in behind the defence.
The first half ended with Mertens slicing a volley wide from the edge of the penalty area after being picked out by a lovely cross from De Bruyne.
Mertens opened the scoring with a sublime dipping volley from the right side of the penalty area two minutes after the break.
De Bruyne curled a free-kick wide as Belgium looked for a quick second goal but Panama could have been level had Thibaut Courtois not been quickly out to deny Michael Murillo after he had escaped the attention of Carrasco.
It was not until the 69th minute that Belgium had the breathing space they craved when Lukaku headed home De Bruyne’s delightful cross with the outside of his foot.
Six minutes later, Lukaku latched on to Hazard’s perfect pass to lift the ball over Penedo and give the scoreline a more convincing look.