Grant Hanley scored his first goal for Scotland but it wasn't enough as they tasted defeat once more.
The Rovers defender headed the Scots in front against Wales on the stroke of half-time at Hampden and it looked like it would be enough to earn Gordon Strachan his first win as Scotland manager.
However two goals in two minutes from the Welsh saw the match turn on it's head. Aaron Ramsey making no mistake with a 73rd minute penalty after Robert Snodgrass had been red-carded.
Sixty seconds later it got worse for the home side as Hal Robson-Kanu got on the end of an Andy King centre to complete the turnaround for Chris Coleman's side.
Jordan Rhodes came on with just four minutes left of the qualifier but could make little impact at a snowy Hampden Park.
The result, a near carbon-copy of when the two sides met in Cardiff back in October, means Scotland still sit bottom of the World Cup group without a win.
Elsewhere it was a disappointing night for Joshua King's Norway as they were on the end of a surprise 1-0 home defeat to Albania.
King started the match in Olso on the bench and was introduced just past the hour mark at the Ullevaal Stadium, the only goal of the game coming on 67 minutes from Hamdi Salihi.
Albania were reduced to ten men in the closing stages but the home side couldn't take advantage of the numerical advantage and in doing so failed to close the gap on group leaders Switzerland.
Earlier in the day New Zealand qualified for the World Cup play-offs following a last-gasp 2-1 win over New Caledonian in Dunedin.
Chris Killen had given the All Whites a tenth minute lead but Cesar Lolohea levelled after the break for Caledonian.
The game looked to be heading towards a draw until Ipswich Town defender Tommy Smith struck a last-gasp goal four minutes into added time to seal the victory for the home side. Rovers' midfielder Tim Payne played the last twenty minutes after being introduced as a second half substitute.
The win means New Zealand have earned a place in a World Cup play-off against a team from the CONCACAF section over two legs next November for a place in the 2014 finals in Brazil.