The founder of the monastery, Varsonofy, spent several years in captivity among the Crimean Tatars in his youth, which allowed him to speak the Tatar language fluently, leading to his transfer to Kazan. Along with him, other monks from the Nikol-Peshnoshsky Monastery arrived in Kazan: Tikhon, Feodorite, Iov, Andronic, Silvester, and monk Simeon from Andronikov Monastery.

Initially, the monastery had two wooden churches: the Preobrazhenskaya, built on a stone foundation with a stone basement, and the Church of Nikolai Ratny, erected in stone in the 1560s. The Church of Nikolai Ratny was built simultaneously with the lower tier of the Spasskaya Tower from Volga limestone. It was a small two-story square church with a long refectory on the west and a semicircular altar projection on the east, a typical Novgorod single-domed temple. The first floor housed the bakery and prosfornia. By 1567, when the first Kazan census book was compiled, the Nikolai Church had already been consecrated and adorned with icons.

Shortly before his death, the first Kazan Archbishop Guriy took monastic vows in the wooden Preobrazhensky Cathedral of the monastery. He was buried on December 5, 1563, behind the altar of the Preobrazhensky Cathedral, and his grave became the first in the Spaso-Preobrazhensky Monastery cemetery. In the following centuries, many notable Kazan residents, priests and professors of the Kazan Spiritual Academy, merchants, military personnel, and officials were buried in the Spassky necropolis.

Over the saint's grave, at the initiative of boyar Ivan Elizarovich Zastolbsky, a "stone cage" was erected. After 12 years of work in the monastery, Archimandrite Varsonofy became a bishop in Tver. In 1571, he returned to Kazan and settled in the monastery he founded. On April 11, 1576, Varsonofy passed away at the age of 81 and was buried next to Saint Guriy.

In 1579, Kazan suffered from a fire, and the wooden Preobrazhenskaya Church burned down. At that time, the Kazan Icon of the Mother of God was found. In 1586, construction began on a new stone Preobrazhensky Cathedral on the site of the fire, which rivaled the cathedral of the Annunciation. The new temple was built on the stone basement of the wooden church, which has survived to this day. In 1595, during construction, the cage of Zastolbsky had to be demolished, and on the same day, October 4, the relics of Saints Guriy and Varsonofy were discovered and transferred to the Preobrazhensky Cathedral.

A small stone "cave" was built in front of the altar of the new cathedral for the remains of monks Iona and Nektariy. Later, Greek hierarch Epiphanius, Archbishop of Jerusalem, Kazan Metropolitan Ephraim, abbots of the monastery Sergey and Yeremey, Greek Bishop Arseniy, and Prince I. E. Bagration-Davidov found their rest there.

In 1901, an extension was made to the western side of the Preobrazhensky Cathedral. In the early 1900s, future missionary Metropolitan Nestor Anisimov served in the monastery.

After the 1917 revolution, the destruction of the Kremlin monastery began. On September 20, 1918, a Red commander announced that the Kremlin was closed to the public and became a military town. On September 22, all Kremlin churches were closed. The nuns of the Kazan Mother of God Monastery carried the relics out of the cathedrals.

During the Soviet era, a military unit was stationed on the territory. The tombstones of the necropolis were destroyed, the cathedral was blown up, and the Church of Saint Cyprian and Justina was demolished. The foundations of some buildings and the brotherhood building remain. The basement of the Preobrazhensky Cathedral and its "cave" have survived under a layer of rubble.

In 1995, during excavations, the relics of Iona and Nektariy of Kazan, as well as Metropolitan Ephraim, were rediscovered. The relics of Varsonofy ended up in the museum's storerooms after the revolution, and their further fate is unknown. Details of the saint's reliquary have been preserved in the collections of the National Museum of Tatarstan.

To this day, the Brotherhood building of the monastery, the basement of the Preobrazhensky Cathedral, the reconstructed Church of Nikolai Ratny, the monastery fence, and the foundations of some buildings have survived.

The barrel and cross vaults of the basement of the Preobrazhensky Cathedral rest on the walls and four columns, with the altar part separated from the main room. The walls and vaults are made of white stone. The vaulted "cave" behind the altar of the cathedral has also survived.

The white stone basement of the Church of Nikolai Ratny from the 16th century has been preserved. The western wall of the church rests on a combat passage between the towers. Decorative sandriks from the 19th century on the windows of the second tier have survived.

The two-story building of the Brotherhood has been restored. A covered gallery connects a series of cell rooms. Adjacent to the building is a three-story treasury house with part of the fence. Arched windows are decorated with trim.

In 2006, Archbishop Anastasius consecrated a chapel in the name of the All-Merciful Savior at the Arsk Cemetery, where some burials found during the excavations and reconstruction of the Kazan Kremlin were transferred.