The ex-Feyenoord star's late leveller sent the match to spot-kicks, and Alvaro Pereira held his nerve to ensure the beaten World Cup semi-finalists claimed the win from 12 yards
A superb run from Edinson Cavani laid on an opportunity for Luis Suarez to break the deadlock eight minutes from time, but Dirk Kuyt's injury-time header sent the match to spot-kicks.
Robin van Persie's wild effort flew over, and Eljero Elia's tame strike allowed Alvao Pereira to slot home the winning kick, and claim the spoils.
Dutch coach Bertvan Marwijk solved his problem of whether to opt for Van Persie or Klaas-Jan Huntelaar in attack, by employing the Arsenal man in a reserved role to accommodate both.
The hosts, meanwhile, started with the potent triumvirate of Diego Forlan, Suarez and Cavani, and it was the latter who squandered the best chance of what was a tepid first half.
Suarez broke on the left-hand side, and floated a cross into the prolific Napoli frontman, but his header lacked power and allowed Erik Pieters to get back on the line to clear the danger.
Oranje were aggrieved not to be awarded a penalty on the half-hour mark, when Diego Lugano appeared to lunge recklessly into a challenge on Van Persie, but despite the protestations of the European side, the referee dismissed their claims.
Van Persie fired over before Cavani had a goal disallowed for offside, and then Afellay went on the break and saw his shot saved by Muslera as the match opened up close to the interval.
The second half was littered with the inevitable substitutions that interrupt the flow of friendly encounters, and both sides struggled to regain their rhythm.
Suarez flicked a header from inside the area that was gathered at the second attempt by Tim Krul, but, with 10 minutes remaining, Uruguay netted a goal to send the packed stadium wild.
A wonderful run by Cavani down the left took him all the way to the byline, and his cut-back was controlled calmly by Suarez, who slotted his finish under the body of Krul at the near post.
However, the Dutch weren't ready to end their mini-South American tour with defeat just yet, and snatched an equaliser in injury time. A corner into the near post found Kuyt, and although the attacker was tightly marked, he managed to shape his header into the net to level the tie to bring on penalties.
Van Persie's kick was blazed wildly over the bar, before Elia's shot was easily read by Muslera. Nicolas Lodeiro's poor strike gave the Dutch a lifeline, but Pereira kept his nerve to net the winning kick, and allow the South Americans a small consolation for their World Cup semi-final defeat in the summer.