The son of Cadwallon ap Cadfan, Cadwaladr was only a child when his father was killed by the army of Oswald of Bernicia at the Battle of Heavenfield, and Cadafael Cadomedd took over in Gwynedd. Raised abroad, either in Ireland, Brittany or in a neighboring Welsh kingdom, Cadwaladr eventually reclaimed his family's throne from Cadafael. He went on to challenge the West Saxons in Somerset in 658, unsuccessfullycitation needed. Cadwaladr was arguably the last Welsh ruler to mount a serious counteroffensive against the Anglo-Saxon forces that had overrun much of Southern Britain since the fall of the Western Roman Empire. It may be for this reason that Geoffrey of Monmouth chose to end his narrative of British kings with Cadwaladr.
After these initial military escapades, Cadwaladr seemingly settled down and focused on the domestic situation, establishing several religious foundations in Gwynedd and gaining a reputation as a devout, pious leader; so much so that, after his death, the Welsh church came to regard him as a saint (he was not canonized).
According to the Annales Cambriae, he died of plague in 682. The earlier Historia Brittonum suggest he was the victim of an earlier plague, in 663/664, but such an early death would seem to extend the reign of his successor, Idwal Iwrch, to an improbable length.