The Dragons paid for an error-prone defensive display and will be desperately disappointed to have now lost two-out-of-two Group A games as White Eagles remain unbeaten
Aleksandar Kolarov and Zoran Tosic gave the hosts a commanding lead with less than 25 minutes played, before Gareth Bale pegged them back with a thunderous free kick.
Filip Djuricic soon restored order, with Dusan Tadic, Branislav Ivanovic and Miralem Sulejmani capping the night off.
Good news ahead of the match for Welsh fans was Liverpool midfielder Joe Allen recovering to full fitness; his inclusion was the only change to Chris Coleman’s team that lost 2-0 to Belgium in Friday’s qualifier.
Lethargic defending was the order of the day for Wales. Simon Church’s reckless foul allowed Manchester City left-back Kolarov to curl a 22-yard free kick inches inside the right-hand post, with Boaz Myhill reacting too slowly to save the 16th-minute strike.
And just eight minutes later, Kolarov wiggled his way into the box from the left with Wales defender stationary - he fell to the floor twice before scrambling to his feet at the left post, and chipped a smart pass sideways for Tosic to lash home his eighth goal for his country from inside the six-yard box.
Wales veered dangerously close to complete capitulation before the break until temporary calm was restored when Milan Bisevac clambered all over winger Bale 30 yards from goal. The Tottenham star’s subsequent free kick was fired excellently into the top-left the goal, leaving Serbian keeper Vladimir Stojkovic stranded and motionless.
However, eight minutes later Darcy Baker’s header was timed poorly and he knocked it backwards, allowing Tadic to slot Djuricic in, who effortlessly restored the two-goal lead by smashing in from the left of goal, 10 yards out.
Coleman tried to change the flow of the game by bringing Adam Matthews off for Sam Ricketts and replaced David Edwards with David Vaughn at half-time, however the momentum remained in the home side’s favour.
Wales were guilty of conceding fouls far too often in their own half and their lack of time on the ball played a large part in why they were unable to break back into the World Cup qualifier.
Tadic, who had been a crucial cog in Serbia’s line-up all match, scored the fourth goal for the hosts in the 55th minute after Chelsea full-back Ivanovic surged forwards down the right to set-up his team-mate’s simple finish in front of goal.
Serbia had won only one of their last 11 internationals but they looked like a nation reborn on Tuesday night and continued to dominate possession and delight their home fans throughout the second half.
Ivanovic further left Welsh emotions in tatters 10 minutes from time by capitalising on Baker’s wayward pass on the edge of the penalty area and slamming a reaction-shot into the bottom right corner.
The hosts eased their foot off the gas for the final minutes but this did not prevent Serbia adding another – substitute Sulejmani looping a deflected shot in from 20 yards with less than a minute left to play.