The Dutch appeared to be on their way to victory after a strong start to the second half, but the PSV winger then helped the Rode Duivels to the win with a sensational outing
Christian Benteke gifted the hosts the lead before the break, but two quickfire strikes from Luciano Narsingh and Klaas-Jan Huntelaar helped the Dutch to a 2-1 lead.
However, goals from Mertens and Romelu Lukaku got the home crowd back on their feet. Jan Vertonghen then poured even more salt Oranje's wounds in the 80th minute.
Both sides created plenty of danger early on, with Vertonghen unleashing a powerful strike for the hosts, while Arjen Robben and Rafael van der Vaart looked dangerous for the Oranje.
Nevertheless, the fans had to wait until the 20th minute for the first big chance of the game, and it immediately resulted in the opener. The Dutch defence allowed Kevin Mirallas too much space down the left wing, and the attacker cut inside before unleashing a low shot that bounced off John Heitinga. Benteke calmly controlled the loose ball and evaded Joris Mathijsen's challenge before firing home.
Holland then took the initiative and came close to levelling the scoring after 28 minutes of play. Narsingh set up Ricardo van Rhijn with a fine low cross, but Thibaut Courtois showed his class with a superb save to prevent the equaliser.
The on-loan Atletico Madrid goalkeeper was again called into action shortly after, this time when Huntelaar tried his luck from inside the box after some good work from Narsingh. However, Courtois once more impressed with a good reflex stop.
There was little Courtois could do about the equaliser shortly after the interval, though. Bruno Martins Indi found Robben with a superb pass down the left, with the latter then sending in a low cross for Narsingh, who tapped home from close range.
Belgium did not have too much time to recover from conceding, as the guests were celebrating once more in the 55th minute, and Martins Indi and Robben were again at the heart of it. The Feyenoord defender set up the Bayern star with an intelligent through pass and the winger then unselfishly squared to Huntelaar. The Schalke star had no trouble finding the empty net from close range, thus scoring his 32nd goal for Oranje.
The home side immediately tried to restore parity, and both Steven Defour and Nacer Chadli tested Maarten Stekelenburg with powerful shots from the edge of the box. The Roma shot-stopper was alert to the danger, though. Kevin De Bruyne, too, came close to restoring parity with a good header, but Stekelenburg once more came out on top.
The Dutch eventually succumbed when Nigel de Jong lost possession inside his own half. Substitute Mertens, who enjoyed an excellent, if brief, spell on the pitch, picked up the loose ball, and beat Stekelenburg with a low shot at the near post.
Things would only get worse for Oranje from there on as they were unable to cope with the energetic Mertens. Only two minutes after the leveller, the PSV man once more escaped the attention of Van Rhijn and set up Lukaku for Belgium's third goal.
A superb Kevin De Bruyne pass toward Mertens then lead to the hosts putting the result beyond doubt, the former Utrecht star controlling the ball, dancing past his marker and then sliding in Vertonghen, who blasted home from inside the area.
Belgium resume match action when they take on Wales on September 7 in their opening 2014 World Cup qualifier, while Netherlands kick off their campaign at home against Turkey on the same night.