Having lost 2-0 to Colombia last week, Belgium were again beaten at the Stade Roi Baudouin, despite taking the lead.
Kevin Mirallas put Belgium ahead after 15 minutes, thanks to an impressive assist from Everton team-mate Romelu Lukaku, but Japan were soon level.
After 37 minutes, Yoichiro Kakitani was perfectly placed to head home a Hiroshi Kiyotaki cross from the right before Keisuke Honda was on target early in the second half.
Substitute Shinji Okazaki rounded off the visitors' scoring, applying a delightful finish to some impressive build-up play with Honda, before Toby Alderweireld headed home 11 minutes from time.
Belgium got off to the ideal start, going ahead through Mirallas after Lukaku had expertly evaded the tackle of Eiji Kawashima before calmly rolling across for Mirallas to finish, with the goalkeeper way out of his box.
They were rewarded for their bright response to going behind when Kakitani headed home the equaliser for Alberto Zaccheroni's men after good work on the right wing from Kiyotaki.
Unmarked, the Cerezo Osaka midfielder comfortably headed home his first international goal since July to restore parity.
Japan came close to going in ahead at the break, with Makoto Hasebe's fierce drive tipped over by Mignolet two minutes before the interval.
Substitute Okazaki gave Japan a two-goal cushion with a well-worked move, playing a neat one-two with Honda before firing past Mignolet in the Belgium goal and, while Alderweireld scored a second for Belgium, it proved insufficient as Japan held on to record their first win in four matches.
