Christian Benteke fired the home side in front in the first half, but the Oranje responded with two quick-fire goals from Luciano Narsingh and Klaas Jan Huntelaar. However, that sparked the beginning of the Mertens show as the winger pulled Belgium level once more before teeing up Romelu Lukaku and Jan Vertonghen in a whirlwind five-minute spell.
Aside from looking to impress under Van Gaal, who took the reins recently following Bert van Marwijk's resignation, the Dutch were also hoping to erase memories of their woeful UEFA EURO 2012 campaign which saw them exit the tournament at the group stage without a point.
However, Belgium were the better side early on and fired a warning to their opponents after ten minutes with a 20-yard drive from Vertonghen, which was well held by visiting goalkeeper Maarten Stekelenburg. The Dutch survived another scare seven minutes later when a troublesome corner from Eden Hazard was headed narrowly over the bar by Daniel Van Buyten.
The home fans sensed a goal was on its way though, and they were proved right after 20 minutes with Benteke getting on the end of a cross from Kevin Mirallas and finishing with his left foot into the bottom corner.
It was the kick Holland needed to get going and Huntelaar almost struck seven minutes later, directing Wesley Sneijder's corner wide with a header. The Oranje came even closer to equalising on the half-hour mark through Nigel de Jong, who let fly with a vicious right-footed shot which was somehow tipped over the bar by home goalkeeper Thibaut Courtois.
Sneijder, who was handed the captain's armband by Van Gaal, tried again for the visitors shortly before the interval, but his effort from 25 yards cleared Courtois' crossbar.
Van Gaal responded to the scoreline by making several changes at the start of the second half, with Bruno Martins Indi, Nick Viergever and Stefan de Vrij coming off the bench to make their international debuts.
And the shake-up did its trick with the Dutch scoring twice in as many minutes. Narsingh grabbed the equaliser after 54 minutes, hammering Arjen Robben's testing cross into the net from the centre of the area. And Robben created their second goal as well with a perfectly weighted pass which Huntelaar finished with a low strike. A third almost arrived after 72 minutes, but Courtois did superbly to tip away Adam Maher's curling shot.
Instead it was the home crowd who were soon celebrating as Belgium hit back with three goals in five minutes thanks to Mertens, who had only come on as a 68th-minute substitute, but could hardly have made more of an impact.
The winger, who plays his club football in the Netherlands with PSV Eindhoven, first slotted the ball beyond the reach of Stekelenburg after 75 minutes to level the scores. Mertens' next shot three minutes later was then punched away by the goalkeeper but straight to the feet of Lukaku, who smashed the ball high into the net from close range.
And Mertens also set up Belgium's fourth ten minutes from time to complete a remarkable turnaround, playing a neat pass into the box for Jan Vertonghen to hit home from ten yards out.