The Blues got off to the toughest possible start, conceding 3 goals early in the first half, and suffered a further blow when Stanley Aborah was red-carded for a two footed tackle on Daniel Kearns.
The home side settled towards the end of the half, with Rory Feely slotting from close range to leave it 3-1 at the break.
Courteney Duffus made it 3-2 early in the second half, but Limerick restored their 2 goal advantage shortly afterwards as former Blues striker Mark O'Sullivan pounced on a breaking ball after a heavy challenge on Dylan Barnett.
Duffus bagged his second of the night to once again restore hope for the home side, but two further goals including a late penalty left it Waterford FC 3 Limerick FC 6 at the final whistle.
The loss marked the end of Waterford's 23 match unbeaten home run at the RSC.