Former champions France prevailed 3-1 in Luxembourg and Euro 2016 winners Portugal beat Hungary 3-0 in World Cup qualifying while the Netherlands crashed 2-0 in Bulgaria and risk missing another big tournament.
An early double from Spas Delev sealed the affair in Sofia as the Dutch, who had failed to qualify for last year's Euro, plunged to fourth place in Group A at the half-way mark of the campaign on Saturday (Sunday AEDT).
"This a nightmare," winger Arjen Robben told Dutch broadcasters NOS.
"We came here with good intentions, and I was optimistic before the match. But the first half level of play was dismal."
The third-place finishers from the 2014 World Cup are six points behind France, three off Sweden, who crushed Belarus 4-0, and also trail Bulgaria by two points.
Only the nine group winners qualify directly for the 2018 finals in Russia, and the eight best second-placed teams determine four further berths in playoff ties.
Elsewhere, Switzerland maintained their perfect record with a 1-0 victory over Latvia, while Begium dropped their first points in a 1-1 home draw with Greece; and tiny Andorra ended a run of 58 straight competitive defeats with a 0-0 draw against the Faroe Islands.
The Dutch fielded 17-year-old debutant Mattijs de Ligt in defence, and he did not look good when Delev opened the scoring five minutes into the game.
Delev struck again in the 20th from long range to add to the woes of the Dutch who saw Bas Dost miss narrowly shortly before halftime.
De Light was taken out of the game at intermission, and veteran Wesley Snijder was one of the new players but the Dutch failed to create a turnaround as the pressure mounts on coach Danny Blind who is in charge since 2015 and failed to qualify for the Euro tournament.
Les Bleus, the beaten Euro 2016 finalists on home soil, were also far from glorious in Luxembourg but retained their three-point lead with victory.
Arsenal's Olivier Giroud opened the scoring in the 28th. Aurelien Joachim levelled with a 34th-minute penalty but Antoine Griezmann restored the lead two minutes later with another spot kick on the other end before Giroud wrapped up matters in the 77th.
In Lisbon, captain Ronaldo scored two cracking goals and took his international tally to 70 in Portugal's crushing win over Hungary.
