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Captain Robbie Keane, vice-captain Shay Given, Damien Duff, Richard Dunne and Ian Harte were among the notable absentees tonight.
Paddy Kenny made his first appearance for 15 months, Aiden McGeady was handed his first start, John O'Shea was switched to centre-back and Steve Finnan to left-back.
Stand-in captain Steven Reid, with just 18 caps over five years, led out his country for the first time, while on the bench the seven remaining players had just 19 caps between them.
Holland fans had criticised Marco van Basten for not taking Klaas Jan Huntelaar to the World Cup, and it was clear to see why as he enjoyed a stunning debut - scoring two and creating two.
After a sluggish start, the writing was on the wall for Ireland from the 20th minute onwards as Holland gathered momentum. In the space of three minutes the imposing Huntelaar had one effort incorrectly ruled out for offside, another blocked by Andy O'Brien, before finally making the breakthrough in the 25th minute.
Television replays showed the Ajax striker was onside when a shot from Chelsea winger Arjen Robben was parried by Kenny before he seemingly poached the opener.
Further disappointment followed for Huntelaar soon after when O'Brien again came to the rescue of a dishevelled-looking defence after Andre Ooijer had split the backline.
But Huntelaar was not to be denied, with the 23-year-old unmarked at the far post in meeting a Robin van Persie corner, with the Republic rearguard all at sea.
A change of formation followed from Staunton, switching from 4-4-2 to 4-5-1, but that mattered little as further misery ensued four minutes from the break.
Sunderland striker Stephen Elliott played a poor backpass into a crowded area, and Huntelaar accepted the gift. With a neat back flick into Robben, the Chelsea winger beat Kenny with a low drive inside the Sheffield United goalkeeper's right-hand post for his eighth goal in 24 appearances.
There were four half-time substitutions, with pacy Newcastle teenager Alan O'Brien handed a debut while O'Shea took up the captaincy from Reid, and momentarily Ireland threatened.
But Holland made it 3-0 in the 53rd minute, initially beating the offside trap before Rafael van der Vaart teed up Huntelaar for an exquisite chip over the advancing Kenny.
Ireland at least then tried to be positive, with Douglas and Andy O'Brien both denied by veteran van der Sar before the rout was completed in the 70th minute.
Running onto a perfectly-weighted through ball from Huntelaar, Robin van Persie drilled home number four in off the underside of the bar.
The Arsenal striker wasted a chance late on for 5-0, sparing Staunton a place in Ireland's record books.