Holland staged an incredible comeback to exact revenge on Spain for their 2010 World Cup Final defeat.
The World Cup holders snatched the lead on 27 minutes when Xabi Alonso converted a spot-kick past Dutch goalkeeper Jasper Cillessen.
Cillessen was a hero on 43 minutes when he stood up to deny Manchester City midfielder David Silva who was clean through and appeared destined to score.
And seconds later Holland were level. Daley Blind hit a superb crossfield ball and Manchester United man Robin van Persie guided up and over Iker Casillas with a deft header.
Then Arjen Robben gave his side the lead on 53 minutes. The former Chelsea man controlled a chipped pass in mid-air and beat two defenders before forcing the ball past Casillas and reeling off to celebrate.
And on 65 minutes Luis van Gaal's side were out of sight when Stefan de Vrij headed home at the far post and Van Persie added a fourth shortly after.
Robben then wrapped up a stunning victory with an emphatic finish after outpacing the Spanish defence to make it 5-1.
Oribe Peralta slots past Charles Itandje
Earlier Mexico went second in Group A after edging out Cameroon 1-0 in their opening match of the tournament at the Arena das Dunas.
The north Americans had two goals disallowed before Oribe Peralta reacted quickest to poke home a rebound.
Mexico first had a goal chalked off when Hector Herrera whipped in a cross from the right and former Tottenham man Giovani Dos Santos volleyed home, only for the linesman's flag to rise.
And Giovani suffered the same fate on 33 minutes when put the ball beyond Cameroon keeper Charles Itandje, this time with his head, only for the same linesman to rule the goal out.
Cameroon thought they had sprung the perfect counter-attack on 59 minutes when Tottenham defender Benoit Assou-Ekotto scuffed a left-footed free-kick that took a wicked deflection and looked like beating Guillermo Ochoa in the Mexico goal. However, the re-directed shot went wide, after wrong-footing the stranded keeper.
Then, on 61 minutes, the relentless and skillful Giovani had another effort on goal that was saved but fell invitingly to the feet of Peralta who poked home to give is side a dream start to the competition.
