Northern Ireland were left 'devastated' after Holland snatched two injury-time goals in Rotterdam to almost certainly end their hopes of qualifying from Group C.
Michael O'Neill appeared to be on the brink of the greatest result of his eight years in charge when substitute Josh Magennis stunned the De Kuip Stadium in the 75th minute.
The Hull City striker, whose only other goal this season came in the Carabao Cup against Preston, climbed to head home at the far post with Northern Ireland's only effort on target after a mix-up between Daley Blind and Matthijs de Ligt allowed Stuart Dallas to cross.
Holland coach Ronald Koeman described the goal as 'an axe in the neck'. Up to that point, Northern Ireland had produced an outstanding defensive performance to frustrate a team ranked third in the world who enjoyed 77 per cent of the possession.
But Holland's pedigree finally told as they hit back to break Northern Ireland hearts and secure a 17th straight win at this ground. The Dutch levelled in the 80th minute when Donyell Malen squared the ball for former Manchester United man Memphis Depay to score.
A draw would still have been a fantastic result for Northern Ireland; one to match the World Cup qualifying point away to Portugal in 2012 and their win over Ukraine at the finals of Euro 2016.
But substitute Luuk de Jong dealt them a sickening blow in the 92nd minute when he scored at the second attempt, and Depay raced through to steer a low shot into the far corner for his second of the night.
Defeat means Northern Ireland must win their remaining games at home to Holland and away to Germany next month, and hope one of the two European heavyweights drop points against Estonia or Belarus.
'We're devastated – it's very harsh on us,' said O'Neill who may be able to plot an alternative route to the finals through a playoff.
'The players knew the significance of a point and we've come away with nothing. We need six points and it's going to be extremely difficult.'
Koeman had called Northern Ireland's players 'fighting machines' beforehand and they certainly lived up that reputation. The size of the task facing Northern Ireland was evident from the team sheet; one side with just three Premier League players against another in which every man is involved in European club competition this season.