ART Grand Prix driver Vandoorne was sluggish away from pole and was instantly overhauled by several rivals, including Rapax driver Sergey Sirotkin who led into La Source.
The Russian then went way too deep into the corner and Vandoorne reclaimed the lead instantly.
Behind him Formula Renault 3.5 championship leader Oliver Rowland, who started second on the grid, was defending from Honda junior Nobuharu Matsushita at La Source.
Vandoorne: I had to dominate GP2
The Japanese driver was left with nowhere to go and hit the back of Rowland, leaving him with a puncture and more than a lap down on the field.
MP driver de Jong's crash then red-flagged the race for 40 minutes.
He had been making a bold move around the outside of Red Bull protege Pierre Gasly at Blanchimont when the pair rubbed wheels, sending de Jong into a ferocious impact with the tyre well.
The Dutchman remained conscious and has been taken to hospital for further checks.
Before the red flag was deployed Vandoorne took advantage of the safety car period to change his tyres, which would prove to be the correct call as the race went on.
Second-place runner Alexander Rossi and Mitch Evans, who moved up to third thanks to a DRS move on Sirotkin down the Kemmel straight, didn't use the chance for a free pitstop.
They had to make a mandatory stop on the race restart, while Vandoorne carved his way through the field with ease to take his fifth win of the season.
Campos Racing driver Arthur Pic claimed his first podium of the season in second ahead of Russian Time's Artem Markelov, who picked up his maiden GP2 podium finish from 22nd on the grid.
Both drivers, like Vandoorne, took advantage of the safety car period to take their mandatory stops and they both managed the tyre degradation perfectly, especially Markelov who enjoyed an eventful race with several close battles.
The Russian was under intense pressure in the closing stages from Carlin driver Julian Leal but he was able to hold on.
Evans and Rossi were left scrapping over fifth, a fight that ended with final-corner contact that will be investigated. Both cut the second part of the chicane before Evans crossed the line ahead.
Jordan King secured eighth and Sunday pole late in the race after pulling off a fantastic switchback overtake on Marlon Stockinger at La Source, but finished way off seventh-placed Nathanael Berthon.
Despite his great start Sirotkin, who pitted late in the race, could only managed ninth ahead of Stockinger.
Other incidents included a La Source clash that ended Nick Yelloly and Matsushita's races, while Norman Nato was ruled out in first-lap contact with Gasly.
Vandoorne seals GP2 title in Russia
Rossi wins after Lynn crashes out