Portugal continued to monopolise possession early in the second period, but struggled to break down their stubborn opponents.
Any hopes of a comeback were ended when Joao Cancelo was shown a second yellow card and sent off for a foul on Tonny Vilhena.
That was the cue for several fans to invade the pitch attempting to take a photo with Real Madrid star Ronaldo, who was duly substituted with 22 minutes to play after failing to score for the first time in 10 matches for club and country.
Ajax teenager Justin Kluivert, the son of former Dutch striker Patrick Kluivert, made his international debut after replacing Depay in the closing stages.
After a low-key affair that was a far cry from the two teams’ infamous ‘Battle of Nuremberg’ at the 2006 World Cup, the Dutch claimed a win they will hope can spur them on to better things having missed out on back-to-back major tournaments.
Portuguese fans will be expecting better when their side take on Spain in their World Cup opener on June 15 in Sochi, before further Group B games against Morocco and Iran.