When Leo died in 912, he was succeeded by his younger brother Alexander, who recalled Nicholas Mystikos and expelled Zoe from the palace. Shortly before his death, Alexander provoked a war with Bulgaria. Zoe returned upon Alexander's death in 913, but Nicholas forced her to enter the convent of St. Euphemia in Constantinople after obtaining the promise of the senate and the clergy not to accept her as empress. However, Nicholas' unpopular concessions to the Bulgarians later in the same year weakened his position and in 914 Zoe was able to overthrow Nicholas and replace him as regent. Nicholas was allowed to remain patriarch after reluctantly recognizing her as empress.

Zoe governed with the support of imperial bureaucrats and the influential general Leo Phokas the Elder, who was her favorite. In 919, there was a coup involving various factions, but the opposition to Zoe and Leo Phokas prevailed; in the end the admiral Romanos Lekapenos took power, married his daughter Helena Lekapene to Constantine VII, and forced Zoe back into the convent of Saint Euphemia.