England were without the suspended Harry Maguire although as Tyrone Mings was handed a start while Jack Grealish kept his spot in the side.
The hosts got off to the perfect start as Youri Tielemans collected a pass from Romelu Lukaku outside the box before firing past Jordan Pickford with a sweet strike.
The lead was doubled in the 23rd minute, with Dries Mertens finding the back of the net with a superb free-kick than left Pickford with no chance.
To make matters worse for England, Gareth Southgate was forced into a change in the 38th minute as the injured Ben Chilwell made way for Bukayo Saka.
The Three Lions looked a little livelier in the second half, with Harry Kane going close with a first-time effort that was saved by Thibaut Courtois on 57 minutes.
With time running out for the visitors, Southgate threw on Jadon Sancho and Dominic Cavlert-Lewin in the 70th minute in an attempt claw their way back into the clash.
Unfortunately, the changes were unable to make the desired impact as England struggled to carve out chances in the attacking third as Belgium held on for the win and a clean sheet.
Roberto Martinez's men sit top of the group, two points ahead England heading into the final group game this week.