According to local legend, recorded in several copies of the 16th-century monument "Tale of the Establishment of Christianity in Murom," the foundation of the monastery is associated with the Murom prince Gleb Vladimirovich, no later than 1015.

Having received Murom in his charge, the holy prince could not live in the city itself due to pagans and established a princely court upstream on the steep wooded bank of the Oka. The appearance of the monastery at the turn of the 10th and 11th centuries is firmly established in Russian historiography, although there are other opinions about the time of its foundation. The monastery is mentioned in chronicles earlier than all other monasteries in Russia and is referenced in the "Tale of Bygone Years" under the year 1096 in connection with the "Murom campaign" of the Chernigov prince Oleg Svyatoslavich and the death of prince Iziaslav Vladimirovich at the walls of Murom.

In the year 6604... Iziaslav gathered an army before the city in the field. Oleg went against him with his troops, and a fierce battle began. Iziaslav, son of Vladimir, grandson of Vsevolod, was killed on September 6... Oleg entered the city, and the townspeople accepted him. Iziaslav was buried in the monastery of St. Savior.

The second mention of the Spassky Monastery as the place of burial of the Murom prince Yuri Vladimirovich, who died on January 19, 1175, refers to this time: "Prince of Murom Yuri passed away on January 19, and was buried at St. Savior in Murom." According to the Ipatiev Chronicle, the church where the prince was buried was built at his initiative: "In the same year, Prince of Murom Yuri passed away on January 19 and was buried at the Church of Christ in Murom, which he himself created."

In the late 15th century, the Spassky Monastery is mentioned in the chronicles in connection with the death of the Novgorod boyar Fyodor Boretsky, who took monastic vows in the Spassky Monastery, the only male monastery in Murom at that time: "That same spring, Fyodor, son of Marfa, passed away in the city of Murom, and took monastic vows on May 9."

In the mid-16th century, after the successful campaign of Ivan IV the Terrible against Kazan, several stone churches were erected in Murom by the order of the tsar, including the main cathedral of the Spaso-Preobrazhensky Monastery.

Despite numerous reconstructions, the cathedral has retained its former appearance. It reflects the tradition of five-domed cathedrals, tracing back to the Assumption Cathedral of the Moscow Kremlin. The modest ornamentation, strict proportions, and monolithic structure give it an appearance of austere simplicity, corresponding to the solemn monastic temple.

The name of Tsar Ivan the Terrible is also associated with the beginning of the economic flourishing of the Spassky Monastery. The tsar endowed the monastery with extensive estates and established a "communal life" there. In the inventories of Murom from 1624 and 1636, 1637, the monastery is listed as "the royal building," confirming the active involvement of the royal family in the life of the monastery. In 1616, Murom was attacked by a Lithuanian detachment commanded by Pan Alexander Lisovsky, during which the Spassky Monastery also suffered. During the church reforms of Patriarch Nikon, Murom long resisted innovations, and the Spassky Monastery became a stronghold of Old Believers. The abbot Archimandrite Anthony wrote several appeals regarding the sign of the cross and sent a petition to Tsar Alexei Mikhailovich pointing out errors in the correction of books under Patriarch Nikon. In 1662, Archimandrite Anthony was removed from the management of the monastery, and in February 1666, he was summoned to a council in Moscow. Despite his repentance, he was exiled to the Kirillo-Belozersky Monastery. In the 1680s, the monastery received significant donations from Metropolitan Varsanofiy Chertkov of Saransk and Podonsk, who came from a dynasty of Murom merchants. With his funds, a two-story abbot's building was constructed, and the reconstruction of the Protection refectory church was initiated. In the 1720s, the monastery was assigned to the Ryazan Archiepiscopal House, and the first school for the education of priestly children was opened on its territory.

On January 26, 1765, a decree from Bishop Pavel Grebnevsky of Vladimir and Murom was sent to the Murom Spiritual Administration about the abolition of the Borisoglebsky Monastery and the transfer of the brotherhood to the Spaso-Preobrazhensky Monastery. The Venerable Seraphim of Sarov visited Elder Anthony Groshovnik here. From 1866 to 1868, the monastery was managed by Archimandrite Gabriel Voskresensky, a professor at Kazan University and the first Russian historian of philosophy. In 1877, Archimandrite Anthony Ilyenov became the abbot, who found the monastery in a deplorable state. After a trip to Mount Athos in 1878, a copy of the icon of the Mother of God "Quick to Hear" was brought to the monastery. In the 1880s, the monastery was restored, and it became a place of pilgrimage.

In 1891, a stone three-story brotherly building was constructed on the territory of the monastery, where Murom vicar bishops were housed. In 1907, a chapel was consecrated in the cell building in honor of the Holy Martyrs of Chersonesus. After the 1917 revolution, the monastery was closed, and the abbot, Bishop Mitrofan Zagorsky of Murom, was accused of complicity in the uprising. In 1918-1919, the Preobrazhensky Cathedral continued to function as a parish church. In the 1920s, the monastery was occupied by the military and the NKVD, and the necropolis began to be destroyed. In April 1990, the public of Murom appealed for the transfer of the monastery to the Russian Orthodox Church. In 1995, the military unit left the monastery, and its revival began. In 2000 and 2009, the monastery was thoroughly restored with the support of the Accounts Chamber of the Russian Federation. On June 22, 2005, a chapel in honor of St. George the Victorious was consecrated on the territory of the monastery.