Wales saw their hopes of World Cup qualification all but ended as Croatia came from a goal down to claim victory at the Liberty Stadium.
Gareth Bale had given Wales the lead from the penalty spot after Dejan Lovren had brought down Joe Ledley.
But goals inside the final 15 minutes from Lovren and Eduardo leave Wales 10 points adrift of the Group A pacesetters with only 12 left on the table for Chris Coleman's side.
The result was poor reward for a fine first-half performance from the hosts, but their inability to retain possession after the break eventually proved costly.
The match had been billed as a battle between star men Bale and Luka Modric, but during the opening half there was only one winner as Wales produced arguably their best half of the campaign.
Bale was inevitably at the centre of their best moments and as early as the sixth minute when ghosting past Modric before being unceremoniously hauled down by Vedran Corluka, who earned a booking for his trouble.
It was part of a sharp start by the hosts, with Jonathan Williams making an impact on his full debut. But it was not without its scares against a Croatia side setting the pace at the top of the group with Belgium.
A James Collins error gave Eduardo a run at goal and Ben Davies did well to block Sammir's shot Boaz Myhill then had to push an Eduardo header off the line from the resulting corner and Wales got the reward for their resilience on 20 minutes.
Ledley exchanged passes with Williams to burst into the box, where he was tripped as he surged past Lovren. Bale took the resulting spot-kick and calmly slotted it down the middle for his 12th goal in 13 games for club and country.
Wales manager Coleman had highlighted the importance of limiting Modric's influence and the hosts were initially up to the task. The Real Madrid midfielder's first major contribution was a long-range shot which deflected harmlessly into Myhill's hands.
The visitors' frustrations grew when Mario Mandzukic wasted a fine chance by firing high and wide having been freed by Eduardo's lofted pass. Wales should have taken advantage of Croatia's failure to take their opportunities, but they spurned their own chances to increase their lead and surprisingly Bale was at fault.
Hal Robson-Kanu broke away down the left and pulled the ball back for Bale on the edge of the box, but Stipe Pletikosa got down low to parry the Tottenham man's effort. An even better chance arrived moments later, Bale this time spooned over the bar after Robson-Kanu had brilliantly switched play having robbed Darijo Srna of possession.
Wales led at the break but the chances Croatia had crafted before the interval suggested a testing second half lay ahead, and the visitors enjoyed an extended spell of pressure on the resumption.
Eduardo wasted another presentable chance after Collins had got underneath a Modric corner, the striker heading wide at the far post with no defenders near him.
Myhill did brilliantly to acrobatically tip Srna's shot over the bar after it had taken a deflection right in front of him on the hour.
Modric was now enjoying the run of midfield and the incessant pressure told with 13 minutes to go, but the goal was down to a misjudgement from Myhill. Lovren's shot looked to be easy enough for the West Brom number one to save, but he failed to get behind it and it flew beyond him into the corner of the net.
Substitute Ivica Olic fired well over from Ivan Rakitic's smart set-up, but the turnaround was completed when Eduardo volleyed home three minutes from time from a similar position to the chance Olic had missed moments earlier.