The monastery was founded by Tsar Ivan the Terrible on October 15, 1552, after the capture of the city. It was built on the site where the royal tent and field church were located, and where Russian soldiers who died at the walls of Kazan were buried. In 1559, the flooding of the Volga destroyed the monastery walls, and it was relocated to the top of the mountain. The monastery is surrounded by a stone wall. Its unofficial name 'Zilantov' is associated with the mountain where, according to legend, the mythical winged serpent Zilant lived.

The foundation of the monastery is also linked to the burial of 'the first holy martyr of Christ in the Kazan land,' John of Kazan.

The main ensemble of the monastery was formed in the 17th century. It included the Uspensky Cathedral of 1625, the church in the name of Metropolitan Alexius of 1720, as well as residential and economic buildings. In 1640 and 1642, the Suzdal bishop Joseph, accused of heresy, was exiled to the monastery.

In 1732 and 1740, the Kazan Spiritual Seminary was located in the monastery, and from 1740, the New-Baptized School. Later, both educational institutions moved to their own buildings. In 1829 and 1850, the archimandrite Gabriel, the author of the first multi-volume history of philosophy in Russia, served as the abbot of the monastery.

In 1918, ten monks of the Zilantov Monastery, including the archimandrite, were shot without trial or investigation on unclear charges of firing at the Red Guards. For some time, the monastery did not function, but soon a Orthodox community was established based on it, which lasted until 1928 when it was liquidated. During the Soviet era, the ensemble on Zilantov Mountain was almost completely destroyed. The monastery cemetery, where notable citizens were buried, was demolished in the 1930s.

In 1998, the former men's monastery was revived as a women's monastery. Only the All Saints Church of 1681, significantly rebuilt in the 1890s, and the abbot's building from the early 19th century remain from the old monastery. Other monastery buildings have appeared in recent decades, including the Trinity Cathedral consecrated in 2006, which is an exact copy of the cathedral of the same name from the Trinity-Sergius Lavra.