A play-off place was already out of reach for Serbia given their failure to rein in Balkan rivals Croatia, with last year's defeat in Macedonia also proving critical.
They got their revenge as Dusan Basta, Aleksandar Kolarov, Dusan Tadic and Stefan Scepovic followed up Stefan Ristovski's early own-goal, before Adis Jahovic squeezed home a late consolation.
Ristovski inadvertently set Serbia on their way in the 17th minute when fumbling the ball past Tome Pacovski and two minutes later Basta clipped Kolarov's cross beyond the Macedonia goalkeeper.
In the 37th minute, Kolarov scored a penalty after Boban Grncarov fouled Branislav Ivanovic.
Basta turned provider after the break, Tadic converting his cross on 54 minutes to make it 4-0 and the Udinese winger picked out Stefan Scepovic's head for goal number five in the 73rd minute.
Jahovic pulled one back for Macedonia seven minutes from time but the basement boys were well beaten.