Rhys was born in present-day Carmarthenshire, the son of Tewdwr ap Cadell. He claimed the throne of Deheubarth following the death of his second cousin Rhys ab Owain in battle against Caradog ap Gruffydd in 1078.
With his wife Gwladus of Deheubarth, daughter of Rhiwallon ap Cynfyn of the Mathrafal dynasty of Powys, he had four sons, Gruffydd, Hywel ap Rhys, Goronwy and Cadwgan, and several daughters, including Nest. Nest was a legendary beauty whose abduction from the castle of her husband Gerald of Windsor at Cenarth Bychan by her cousin Owain ap Cadwgan would start a civil war.
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, but with a major show of power as well, traversing the width of Wales, and it seems likely he came to an arrangement with Rhys, whereby Rhys paid him homage and was confirmed in possession of Deheubarth. Rhys paid William 40 pounds a year for his kingdom, ensuring good future relations with William that lasted until the end of his lifetime. Rhys was content as the arrangement meant that he only had to deal with the jealousy of his fellow Welsh princes.
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 Mardudd ob 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 the increasing Norman pressure following the end of William's reign in 1087 until he was killed at the Battle of Brecon in April 1093 by the Normans led by Bernard de Neufmarché, lord of Brecknock.
Rhys's son Gruffydd inherited some of Deheubarth, but Rhys's death led to the Normans taking over much of the kingdom, with Gruffydd being left to rule a much smaller area.