Pablo Sarabia (L) scored from the penalty spot in the first half in Athens to earn Spain their winWales are officially guaranteed at least a place in the World Cup play-offs after Spain beat Greece 1-0.
Wales started their qualifying campaign knowing they had all but secured a play-off spot having won their Nations League group.
Spain's win in Athens formally seals it, even if Wales finish outside the top two in their qualifying group.
Wales must finish second to have any chance of being seeded for March's play-offs.
Teams who reach the play-offs via the Nations League are unseeded and will be away in their semi-final to a seeded nation.
Wales can guarantee a top-two finish with four points from their final two qualifiers at home to Belarus on Saturday and Belgium on Tuesday.
Wales could theoretically qualify automatically - they are five points behind Group E leaders Belgium with two games to go - but they would need the world's number one ranked side to lose to Estonia as well as to Rob Page's men in Cardiff.
If Wales beat Belarus and lose to Belgium - and the Czech Republic beat Estonia in their only remaining game - the play-off spot would go down to goal difference. The Czechs are currently two ahead on that metric.
Even if Wales do finish outside the top two, they now have a play-off place guaranteed.
Spain's victory, secured by Pablo Sarabia's goal, means they need a point from their showdown with Sweden at the weekend to secure a place at next year's World Cup finals.
Sweden had led Group B going into the final two games but a shock 2-0 loss in Georgia earlier has handed Spain the advantage.
How did Spain confirm Wales' play-off place?
Wales are the fifth best ranked Nations League side, with two play-off places given to the highest ranked sides who do not finish in the top two of their qualifying group.
Belgium and Italy had already guaranteed top-two spots in their groups, leaving only France and Spain above Wales.
As Spain avoided defeat against Greece on Thursday, they secured at least a second-place finish in Group B, meaning Wales will definitely be in the play-offs whatever happens in their qualifying group.
It is significant for Wales, who have not played at a World Cup since 1958, when they also qualified via play-offs.
