With the death of Pepin in 640, Grimoald became the head of his household, the most powerful in Austrasia. At this time, Radulf, Duke of Thuringia, rebelled against Sigebert III, king of Austrasia. Grimoald participated in the ensuing expedition against the insurrection, but it was a failure. Nevertheless, Grimoald succeeded in saving the life of the king and became his close friend. Then, by removing the mayor of the palace, Otto, he took over the position which his father once held.
Grimoald convinced the childless king (Sigebert III) to adopt his son, named Childebert at his baptism. Sigebert eventually had an heir, Dagobert II, but Grimoald feared the fate of his own dynasty and exiled the young Dagobert to either an Irish monastery or the cathedral school of Poitiers. Upon Sigebert's death, probably in 651, Grimoald put his son on the throne.
Grimoald was deposed and executed by the king of Neustria, who thereby reunited the Kingdom of the Franks. The Liber Historiae Francorum tells that Clovis II had captured and executed him by 657 (subsequently treating Clovis' reign with hostility and his son Chlothar's reign with disdain).