Following the death of Gruffydd's father Rhys ap Tewdwr in 1093, Deheubarth was taken over by the Normans, and Gruffydd spent much of his early years in exile in Ireland.
He returned about 1113, and after several years of wandering from place to place was able to raise enough men to attack a number of Norman castles and towns in 1116 with some success. However an attack on Aberystwyth was defeated and Gruffydd's army dispersed.
Gruffydd came to terms with King Henry I of England and was allowed to rule a portion of his father's kingdom, the Cantref Mawr, although he was soon under pressure from the Normans again and was forced to flee to Ireland for a period in 1127.
Gruffydd himself with Owain and Cadwaladr gained a crushing victory over the Normans at Crug Mawr near Cardigan the same year.
In 1137 Gruffydd gained further success in Dyfed, but died shortly afterwards in uncertain circumstances.
Gruffydd had four sons by Gwenllian ferch Gruffydd, Maredudd, Rhys, Morgan and Maelgwn. He also had two older sons by a previous marriage, Anarawd and Cadell, and at least two daughters, Gwladus and Nest. He was followed by his eldest son, Anarawd. Of his other sons, Cadell, Maredydd and Rhys (later known as The Lord Rhys) all ruled Deheubarth in turn.