Goals from Filip Dordevic, Aleksandar Kolarov and Lazar Markovic ensured the Dragons dropped to the bottom of World Cup qualifying Group A and never looked like avenging the 6-1 mauling at the hands of the same opponents in Novi Sad a year ago.
The result was their biggest home defeat in a competitive match for seven years and also their ninth defeat in the last 13 internationals.
The visitors broke the deadlock through Dordevic inside the opening eight minutes.
Lazar Markovic’s initial header was parried up into the air by Boaz Myhill, but the 25-year-old, who plays his football for Ligue 1 side Nantes, headed the ball back across goal and into the far corner.
Serbia came into the game having not won any of their last five competitive away games, stretching back two years, but they doubled the lead seven minutes before the break thanks to a stunning strike from Kolarov.
The Manchester City man picked up the ball about 30 yards from goal before unleashing a piledriver of a left-foot strike which flew into the top right-hand corner.
It was all over 10 minutes into the second half when Dusan Tadic’s effort was palmed out by Myhill only to Markovic who made no mistake from close range.
Bale, who joined Real Madrid in an astronomical £85.3m deal from Tottenham this summer, was playing his first match after suffering a groin injury in pre-season.
He very nearly got his name on the scoresheet with a trademark free-kick, but it was tipped over the crossbar.
Inside three minutes a poor touch from Andrew Crofts gifted the Serbs the ball on the edge of the Welsh box, but Markovic spooned an effort wastefully wide.
But there was no reprieve in the eighth minute as Wales fell behind.
Kolarov whipped in a cross from the left, after Crofts had played him onside, which Filip Djuricic headed straight at Myhill, but Djordjevic headed in the rebound with no Wales defender in sight.
Dusan Tadic could have made matters worse for Wales had he not driven his shot straight at Markovic when left unmarked at a corner, while Branislav Ivanovic put a free header well wide from a Kolarov corner.
Captain Aaron Ramsey was the best player on the pitch by some distance, and his link-ups with Craig Bellamy proved Wales’ best attacking outlet.
The Arsenal midfielder almost rounded off an excellent Welsh counter, but Vladimir Stojkovic was out of his goal quickly to snatch the ball off his head.
But they were soon on the defensive again as another Crofts error gave Ljubomir Fejsa a sight of goal only for Myhill to save, but the goalkeeper then stood no chance when Kolarov deposited an unstoppable drive into the top corner to double the visitors’ lead.
Welsh woes were compounded when Sam Vokes headed inches wide from close range.
They then fell 3-0 behind 10 minutes into the second half. An overworked Myhill superbly saved Kolarov’s shot, but no-one reacted quickly enough to prevent Markovic putting away the rebound.
Boos rang out around the Cardiff City Stadium and Chris Coleman, perhaps sensing the mood, quickly readied Bale, who came on in place of Vokes for his first action since becoming the world’s most expensive player.
He quickly had two shots on goal, with Stojkovic beating away one fierce drive and Bale putting the rebound wide.
During a meandering final quarter Bale was the only real point of interest.
One lovely, balanced run was halted as he went down, and was ordered to his feet by the referee.
Bale then almost scored with a sensational swerving and dipping free-kick which Stojkovic just about tipped over.