On the death of his father in 511 he received as his share of the kingdom the town of Soissons, which he made his capital, the cities of Laon, Noyon, Cambrai and Maastricht, and the lower course of the Meuse River. But he was very ambitious, and sought to extend his domain.

He was the chief instigator of the murder of his brother Chlodomer's children in 524, and his share of the spoils consisted of the cities of Tours and Poitiers. He took part in the various expeditions against Burgundy, and after the destruction of that kingdom in 534 obtained Grenoble, Die and some of the neighbouring cities.

When Provence was ceded to the Franks by the Ostrogoths, he received the cities of Orange, Carpentras and Gap. In 531 he marched against the Thuringii with his brother Theuderich (Thierry) I, and in 542 with his brother Childebert I against the Visigoths of Spain. On the death of his great-nephew Theodebald in 555, Clotaire annexed his territories; and on Childebert's death in 558 he became king of all Gaul.

He also ruled over the greater part of Germany, made expeditions into Saxony, and for some time exacted from the Saxons an annual tribute of 500 cows. The end of his reign was troubled by internal dissensions, his son Chram rising against him on several occasions. Following Chram into Brittany, where the rebel had taken refuge, Clotaire shut him up with his wife and children in a cottage, to which he set fire. Overwhelmed with remorse, he went to Tours to implore forgiveness at the tomb of St Martin, and died shortly afterwards.