Rhys claimed the throne of Deheubarth following the death of his second cousin Rhys ab Owain in battle against Caradog ap Gruffydd in 1078. In 1081 Caradog ap Gruffydd invaded Deheubarth and drove Rhys to seek sanctuary in the St David's Cathedral. Rhys however made an alliance with Gruffydd ap Cynan who was seeking to regain the throne of Gwynedd, and at the battle of Mynydd Carn in the same year they defeated and killed Caradog ap Gruffydd and his allies Trahaearn ap Caradog of Gwynedd and Meilyr ap Rhiwallon. The same year William the Conqueror visited Deheubarth, ostensibly on a pilgrimage to St David's, though it seems likely he came to an arrangement with Rhys, whereby Rhys paid him homage and was confirmed in possession of Deheubarth.
In 1088 Cadwgan ap Bleddyn of Powys attacked Deheubarth and forced Rhys to flee to Ireland. However Rhys returned later the same year with a fleet from Ireland and defeated the men of Powys in a battle in which two of Cadwgan's brothers, Madog and Rhiryd, were killed.
In 1091 he faced another challenge in the form of an attempt to put Gruffydd, the son of Maredudd ab Owain on the throne of Deheubarth. Rhys was able to defeat the rebels in a battle at St. Dogmaels, killing Gruffydd.
Rhys was able to withstand increasing Norman pressure until 1093, when he was killed near Brecon by the Norman invaders of that area, either in battle or by treachery. He was married to Gwladys verch Rhiwallon of the Mathrafal dynasty of Powys, by whom he had two sons, Gruffydd and Hywel, and a daughter Nest. Gruffydd inherited some of Deheubarth, but Rhys' death led to the Normans taking over much of the kingdom, with Gruffydd ruling only a much smaller area.
His daughter, Nest verch Rhys, was of legendary beauty. She was married to Gerald of Pembroke and is sometimes known as the "Helen of Wales", as her abduction from her husband's castle at Cenarth Bychan (probably Cilgerran Castle) by Owain ap Cadwgan, son of his old enemy, Cadwgan ap Bleddyn, started a civil war.