The result left the Belgians joint top of the group with seven points from three games along with Croatia, who came from behind to win 2-1 at fellow former Yugoslavs Macedonia.
Serbia, whose inexperienced team showed plenty of potential but also a lack of steel at the back, have four points from three games and now face a crunch visit to neighbours Macedonia on Tuesday.
The home side were punished for missing a hatful of chances when the score was level and after Belgium broke the deadlock against the run of play, Serbia struggled to keep up their momentum as the physically stronger visitors ran them ragged on a slippery turf in Red Star's stadium.
Roared on by 18,000 fans who turned up in driving rain, Serbia made a bright start and twice came close in the opening minutes after Zoran Tosic hit the post and Dusan Tadic saw his bouncing shot saved by Belgium keeper Thibaut Courtois.
Captain Branislav Ivanovic, who had a tense personal battle with his Chelsea team-mate Eden Hazard, then failed to connect on Tosic's stinging low cross from the right which flashed across the face of goal.
Zeljko Brkic did well to keep out a Benteke effort from a tight angle at the other end moments later but was powerless in the 34th minute, when the Belgian striker headed Nacer Chadli's teasing cross from the right into the roof of the net.
The lively Tosic, who was a handful for his markers on either flank, spurned a good chance to put Serbia back on level terms before the break, firing wide with his weaker, right foot from eight metres.
For all his tireless running and close control, the former Manchester United winger was again guilty of poor finishing shortly after the break as he scuffed a weak shot well wide from a good position.
Hazard should have made it 2-0 at the other end several minutes later, but Brkic did well to recover and palm away the midfielder's dinked shot after Chadli sent him clear with a defence-splitting pass.
Gaps in Serbia's tiring 4-2-3-1 formation began to open up as Belgian substitute Dries Mertens, who replaced Hazard, missed another chance for the visitors.
Belgium looked the more confident and composed team and it was no surprise when they doubled their lead midway through the second half as right winger De Bruyne broke through the middle and beat Brkic with a low shot from 13 metres.
Courtois parried a stinging shot by substitute Marko Scepovic as Serbia pressed forward in vain and De Bruyne nearly added a third for Belgium shortly afterwards, hitting the side netting from close range.
Everton striker Mirallas came on for de Bruyne in the dying minutes but made an immediate impact, side-footing home a pinpoint Mertens cross from the left in stoppage time.
