The principal wars in which Anastasius was engaged were those known as the Isaurian and the Persian. The former (492-496) was stirred up by the supporters of Longinus, the brother of Zeno. The victory of Cotyaeum in 493 "broke the back" of the revolt, but a guerrilla warfare continued in the Isaurian mountains for some years longer. In the war with Persia (502-505), Theodosiopolis and Amida were captured by the enemy, but the Persian provinces also suffered severely and the Romans recovered Amida. Both adversaries were exhausted when peace was made (506) on the basis of status quo. Anastasius afterwards built the strong fortress of Daras to hold Nisibis in check. The Balkan provinces were devastated by invasions of Slavs and Bulgarians; to protect Constantinople and its vicinity against them he built the "Anastasian wall," extending from the Propontis to the Euxine.
The emperor was a convinced Monophysite, but his ecclesiastical policy was moderate; he endeavoured to maintain the principle of the Henotikon of Zeno and the peace of the church. It was the uncompromising attitude of the orthodox extremists, and the rebellious demonstrations of the Byzantine populace, that drove him in 512 to abandon this policy and adopt a monophysitic programme. His consequent unpopularity in the European provinces was utilized by an ambitious man, named Vitalian, to organize a dangerous rebellion, in which he was assisted by a horde of "Huns" (514-515); it was finally suppressed by a naval victory won by the general Marinus. The financial policy of Anastasius was so prudent and economical that it gained him a reputation for avarice and contributed to his unpopularity. He died in 518.