The two European heavyweight nations locked horns at the King Baudouin Stadium in Brussels in their opening Group A4 clash.
In front of their home fans, De Bruyne and his Red Devils colleagues were hoping to get their Nations League campaign off to a winning start.
Instead, however, it was a Dutch side featuring Ake at the heart of its defence who secured all three points in dominant fashion thanks to a first half strike from Steven Bergwijn and further efforts after the break from Memphis Depay (2) and Denzel Dumfries.
Belgian substitute Michy Batshuayi struck in injury time to provide a morsel of consolation for the hosts.
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While Roberto Martinez’s side struggled to find any consistency and rhythm, Louis van Gaal’s Dutch were in superb form.
A dominant first half display was rewarded on 40 minutes when Spurs star Bergwijn fired a swerving shot into the corner of the Belgium net.
The Netherlands then doubled their advantage on 51 minutes through Depay, the Barcelona winger sent clear through the middle before firing past Simon Mignolet.
The Dutch further extend their lead on the hour when Mignolet palmed away Berghuis’ shot but Daley Blind picked up the loose ball before crossing for Denzel Dumfries to finish.
Six minutes later Depay then claimed his second goal of the night and the Netherlands’ fourth, finishing superbly after Blind had headed down Virgil van Dijk’s chipped ball forward.
It was a miserable night for Belgium who also saw Romelu Lukaku forced off with injury and their gloom was further compounded when Timothy Castagne’s effort was disallowed for offside after a VAR check.
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However Batshuayi did fire home at the far post in injury time but it was scant consolation.
De Bruyne played the full 90 minutes for Belgium while Ake was replaced by Matthijs de Ligt on 74 minutes.
The result leaves the Netherlands top of Group A4 with three points on goal difference from Poland. Belgium and Wales are both without a point.
Group A4 action resumes on Wednesday when Belgium host Poland and the Netherlands visit Wales.
