Otto III (980-1002) was the only son of Emperor Otto II and Empress Theophanu. Otto became King of Germany at the age of three in 983, after his father's death, but his young age meant that various regents ruled in his name. Initially his mother, Empress Theophanu served as regent for her son until her death in 991. His grandmother, Dowager Empress Adelaide of Italy served as regent until 994, when Otto was finally eligible to rule.

In 996, Otto marched to Italy and claimed the titles of Holy Roman Emperor and King of Italy for himself, as well as to reestablish Imperial control over the city of Rome, which had revolted. He quickly put down the rebellion and installed his own cousin as the new pope, but soon had to return when the papacy rebelled again, reinstalling his cousin and executing the traitors. His actions strengthened Imperial control over the Catholic Church.

Otto improved the Holy Roman Empire's relations with Bohemia, Hungary and Poland, extending the influence of Christianity into Eastern Europe. While he was returning to Rome in 1001, another rebellion by the Roman aristocracy occurred, forcing him to flee the city. He died of a sudden fever a year later while marching back to reclaim the city, leaving no clear heir to succeed him and throwing the Empire into political crisis once more.