The Netherlands dampened Wales' World Cup qualification party with a late Nations League victory in Cardiff.
Still riding the wave of celebrations after Sunday's play-off final win over Ukraine, Rob Page's much-changed side started brightly as they searched for a first win in the Nations League top tier.
Dutch boss Louis van Gaal named a completely different starting XI to their 4-1 thumping of Belgium last time out, but Teun Koopmeiners's strike gave them the lead early in the second half.
Rhys Norrington-Davies thought he had earned Wales a point when his injury-time header made it 1-1, but 100 seconds later Burnley's Wout Weghorst nodded home to silence the Welsh crowd.
Victory for Netherlands moves them top of Group A4 in the Nations League, while Wales remain bottom of the four teams after back-to-back defeats in the competition.
Norrington-Davies impresses for much-changed Wales
Sunday's World Cup play-off final match against Ukraine was always the priority for Wales going into this extended international break.
The seven changes made by Page highlighted that, with influential figures Aaron Ramsey, Joe Allen and Sunday's goalkeeper hero Wayne Hennessey all left out of the matchday squad, with Gareth Bale coming on as a late substitute.
Despite that, and much like last week's loss against Poland, Wales again went toe-to-toe against one of the world's football heavyweights.
Wales' first real chance came after 13 minutes, the ever-busy Norrington-Davies and Harry Wilson combined well to win a corner and from the resulting cross the Fulham man nodded just wide at the back post.
Centre back Chris Mepham almost provided an unlikely assist when his deep cross was floated perfectly for Norrington-Davies, who rose above Jordan Teze but put his header over the bar.
Netherlands goalkeeper Mark Flekken was almost left red-faced when he hesitated over a clearance and was charged down by Dan James, but the Leeds winger's deflected attempt sailed behind for a goal-kick.
Norrington-Davies continued to cause problems and picked up a loose ball outside the Dutch penalty area before drawing a foul in a dangerous position.
Dead-ball specialist Wilson claimed the ball immediately and forced a diving save out of Freiburg stopper Flekken, who pushed the ball safely away.
Koopmeiners turns on Dutch style
After James forced another comfortable save the Dutch got a foothold in the game.
A few half-chances came and went, before a deep run from Koopmeiners was not tracked by the Welsh defence, but Ben Davies - who made countless blocks against Ukraine on Sunday - stretched to make a goal-saving tackle.
Seconds before half-time the Netherlands had the best chance of the opening period, when Cody Gakpo took advantage of a misread defensive header to race clear of Davies and Mepham.
The PSV striker cut back well onto his right foot, but his goal-bound effort was blocked by Mepham and bounced narrowly wide of the left post.
The Netherlands started the second half as they ended the first and opened the scoring five minutes after the restart.
Debutant Jerdy Schouten and Koopmeiners were afforded too much space on the edge of the Wales box and the Atalanta midfielder's low driving shot beat Adam Davies - who had replaced Danny Ward in the Welsh goal at the break.
Wales responded to going behind well, Rubin Colwill and Matt Smith coming on, but they failed to test Flekken as they did in the first half.
That was until Connor Roberts broke down the Wales right and crossed to the back post, where Norrington-Davies rose highest.
The wing-back's goal looked to have sealed a draw for Wales and ensure World Cup qualification celebrations continued, but Netherlands had other plans.
Burnley striker Weghorst's diving header less than two minutes after Wales' equaliser beat a full-stretch Davies to send the 600-strong contingent of travelling fans back into full voice.
Line-ups
Wales
Formation 5-3-2
12Ward
14Roberts5Mepham6Rodon4Davies17Norrington-Davies
3Levitt16Morrell8Wilson
9Johnson20James
12WardSubstituted forDaviesat 45'minutes14Roberts5Mepham6Rodon4Davies17Norrington-Davies3LevittSubstituted forSmithat 67'minutes16MorrellSubstituted forColwillat 60'minutes8Wilson9JohnsonSubstituted forBaleat 77'minutes20JamesSubstituted forMatondoat 77'minutesSubstitutes
2Gunter7Smith10Burns11Bale13Colwill15Ampadu18Williams19M Harris21Davies22Thomas23MatondoNetherlands
Formation 3-4-2-1
13Flekken
2Teze6de Vrij3de Ligt
15Hateboer20Koopmeiners18Schouten16Malacia
12Lang9Gakpo
19Weghorst
13Flekken2TezeBooked at 3mins6de Vrij3de LigtSubstituted forMartins Indiat 84'minutes15Hateboer20Koopmeiners18SchoutenSubstituted forde Jongat 67'minutes16Malacia12LangSubstituted forTilat 90+1'minutes9GakpoSubstituted forBergwijnat 67'minutes19WeghorstSubstitutes
1Cillessen4Martins Indi5Aké7Bergwijn8Til10Depay11Berghuis14Klaassen17Blind21de Jong22Dumfries23ScherpenLive Text
Match ends, Wales 1, Netherlands 2.
Second Half ends, Wales 1, Netherlands 2.
Goal! Wales 1, Netherlands 2. Wout Weghorst (Netherlands) header from the centre of the box to the top left corner. Assisted by Tyrell Malacia with a cross.
Goal! Wales 1, Netherlands 1. Rhys Norrington-Davies (Wales) header from the centre of the box to the top left corner. Assisted by Connor Roberts with a cross.
Attempt blocked. Rubin Colwill (Wales) right footed shot from the right side of the box is blocked. Assisted by Connor Roberts.
Substitution, Netherlands. Guus Til replaces Noa Lang because of an injury.
Offside, Netherlands. Jordan Teze tries a through ball, but Steven Bergwijn is caught offside.
Tyrell Malacia (Netherlands) wins a free kick in the defensive half.
Foul by Gareth Bale (Wales).
Foul by Wout Weghorst (Netherlands).
Chris Mepham (Wales) wins a free kick in the defensive half.
Foul by Stefan de Vrij (Netherlands).
Rabbi Matondo (Wales) wins a free kick in the attacking half.
Substitution, Netherlands. Bruno Martins Indi replaces Matthijs de Ligt because of an injury.
Corner, Netherlands. Conceded by Joe Rodon.
Substitution, Wales. Gareth Bale replaces Brennan Johnson.
Substitution, Wales. Rabbi Matondo replaces Daniel James.
Corner, Wales. Conceded by Tyrell Malacia.
Hand ball by Noa Lang (Netherlands).
Jordan Teze (Netherlands) wins a free kick in the defensive half.