The Dutch captain, who signed for Paris Saint-Germain from Liverpool just before the tournament began, scored twice in the second half at the Johan Cruyff Arena after Memphis Depay had put them in front.
Depay, fresh from sealing a transfer of his own to Barcelona, could claim assists for both of Wijnaldum's goals as Frank de Boer's side made it nine points out of nine in Group C.
They had already secured qualification for the last 16 as group winners after defeating Ukraine and Austria in front of their own fans at the home of Ajax, and so the 1988 European champions knew they were heading for a knockout tie in Budapest next weekend.
North Macedonia, meanwhile, were already out after losing their first two games in their debut appearance at a major tournament.
They leave without a point, but they will never forget this campaign and this game will be best remembered as the last of veteran 37-year-old striker Goran Pandev's international career after two decades.
He was gifted a Dutch shirt with the number 122 – the number of caps he has won – before kick-off, and was given a guard of honour by his teammates as well as an ovation from the home fans on being replaced midway through the second half.
But the North Macedonians couldn't sign off on a high, with Pandev setting up Aleksandar Trajkovski for a shot off the post when the game was still goalless.
They also had two goals disallowed for offside and felt that the Netherlands' opener in the 24th minute should not have stood.
Pandev felt he was fouled on the edge of the Dutch box by Daley Blind but the Romanian referee allowed play to go on and the home side broke forward.
Depay exchanged passes with Donyell Malen before finishing and the goal stood following a VAR check.
RELAXED SEND-OFF
PSV Eindhoven forward Malen and Ajax midfield prodigy Ryan Gravenberch came in for Wout Weghorst and Marten de Roon as the only two changes made to the Dutch line-up by De Boer.
He stuck with his much criticised 3-5-2 formation – before tweaking it in the second half – but was reluctant to rest too many players with six days after this until their next match.
Wearing their black change kit, the Netherlands had VIP support in the shape of Prime Minister Mark Rutte, who watched the game alongside his North Macedonian counterpart Zoran Zaev.
And, despite the cold and damp conditions, the evening had the air of a relaxed send-off for the Dutch side, who will not play any more games in Amsterdam – victory in the last 16 will send them on to a quarterfinal in distant Baku.
After Depay's opener, Denzel Dumfries came close to making it 2-0 before they ran away with the game early in the second half.
Matthijs de Ligt had a header cleared off the line prior to Depay squaring for Wijnaldum to make it 2-0 six minutes into the second period.
Another delightful move brought the third goal just before the hour as Malen's pass found Depay whose shot was saved by Stole Dimitrievski only for Wijnaldum to convert the follow-up for his third of the tournament.
Weghorst then hit the bar within moments of appearing off the bench and the Netherlands look in good shape, albeit with tougher tests lying ahead. (AFP)

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