Maurice's reign was troubled by almost constant warfare. After he became Emperor, he brought the war with Sasanian Persia to a victorious conclusion. The Empire's eastern border in the South Caucasus was vastly expanded and, for the first time in nearly two centuries, the Romans were no longer obliged to pay the Persians thousands of pounds of gold annually for peace. Afterwards Maurice campaigned extensively in the Balkans against the Avars – pushing them back across the Danube by 599. He also conducted campaigns across the Danube, the first Roman Emperor to do so in over two centuries. In the west, he established two large semi-autonomous provinces called exarchates, ruled by exarchs, or viceroys of the emperor. In Italy Maurice established the Exarchate of Italy in 584, the first real effort by the Empire to halt the advance of the Lombards. With the creation of the Exarchate of Africa in 591 he further solidified the power of Constantinople in the western Mediterranean.

Maurice's successes on battlefields and in foreign policy were counterbalanced by mounting financial difficulties of the Empire. Maurice responded in several unpopular measures which alienated both the army and the general populace. In 602 a dissatisfied officer named Phocas usurped the throne, having Maurice and his six sons executed. This event would prove a disaster for the Empire, sparking a twenty-six-year war with Sassanid Persia which would leave both empires devastated prior to the Muslim conquests.