The next wave of invaders to leave their mark were the Anglo-Normans in the twelfth century. When the King of Leinster, Dermot MacMurrough, made his bid for the High Kingship of Ireland, he knew Waterford was strategically vital for control of the southwest. In 1170, he called on his Anglo-Norman allies, the most important of these being the Earl of Pembroke, known as Strongbow , to attack the city. The city walls and towers were formidably strong, but on August 25, the third day of attack, the Normans discovered a weak point, made a breach and flooded in, taking the city with scenes of bloodcurdling violence. Strongbow received his reward: Dermot MacMurrough's daughter Aoife's hand in marriage, and her inheritance. The wedding celebrations took place in Reginald's Tower; the marriage was the first such alliance between a Norman earl and an Irish king, and as such was a crucial and symbolic historical event.

The following year, surprised at Strongbow's success, Henry II arrived with an awesome display of naval strength (400 ships) and gave the Waterford Normans a charter offering protection - his way of ensuring allegiance to the English crown. Subsequent English monarchs maintained this allegiance, and in 1210 King John arrived with a huge army and enlarged the city with new fortifications. The best-preserved towers of these Norman walls are at Railway Square, Castle Street, Stephen Street and Jenkins Lane. Waterford is the oldest continuous urban settlement in Ireland and in that sense can be considered its oldest city. Its proximity to Europe made it a prime port for the important wine trade and it enjoyed royal patronage from the medieval period onwards. In the late fifteenth century it reaped further royal favour through its part in bringing to ground two would-be usurpers threatening Henry VII: first Lambert Simnel in 1487, then Perkin Warbeck eight years later.

Waterford flourished as an important European port into the sixteenth and seventeenth centuries, trading with England, France, Spain and Portugal, and Newfoundland during the eighteenth and early nineteenth centuries, as well as maintaining its inland commerce. It was the only city in Ireland to withstand Cromwell , though his forces returned under the command of General Ireton, who took the city without the usual scenes of carnage, giving its citizens honourable terms. Abundant testimony to the city's eighteenth-century prosperity is evident in both ecclesiastical and secular architecture. However, Waterford is nowadays most famous for its crystal , first produced here in 1783. The factory closed in 1851 but reopened in 1951 and is now one of the city's major employers, as well as being a popular draw for tourists.