His mother Theophanu served as regent until her death in 991. Otto II's mother, Adelaide of Italy then served as regent until Otto III reached his majority.
Otto III strove to make the city of Rome his imperial seat. After the death of his cousin, Pope Gregory V, he secured the election (999) as Pope Sylvester II[?] of his associate (and former tutor) Gerbert of Aurillac.
Otto died childless and was succeeded by his cousin, Henry II.