By the 15th century, the Spaso-Preobrazhensky Monastery already existed thanks to the efforts of Grand Duke Ivan Vasilyevich of Ryazan. For several centuries, it remained wooden, surviving numerous fires and destructions, including during the attack by the troops of Hetman Pyotr Sagaidachny and Prince Vladislav on Pereyaslavl Ryazansky. In 1647, a fire destroyed all the wooden buildings of the Kremlin and the monastery. In the 1640s, the first stone church of the Epiphany of the Lord was built with two chapels in honor of the Protection of the Mother of God and the Apostle John the Theologian, as well as a bell tower with six bells. Little information has survived about the early history of the monastery. It is known that the superiors held significant power. In the 'Additional Information about the Ryazan Diocese,' Archimandrite Hieronymus mentions that the superiors were archimandrites, although the monastery was not considered famous. In 1653, Archimandrites Bogolep and Solotchinsky Sergey received permission to serve in a white hat and use a carpet during the service. The significance of the monastery is confirmed by the participation of its representatives in Councils in Moscow. For example, at the Council of 1589, the archimandrite of the Solotchinsky Monastery from Ryazan was present, and three years later, the Spassky archimandrite was mentioned. Since 1742, archimandrites were granted the right to wear pectoral crosses. From 1868, the monastery was managed by a vicar until 1902, when the see was transferred to the Trinity Monastery, but in 1907 it was returned to the Spassky Monastery. Among the vicar bishops was Isidor, who served from 1906 to 1911 and died in 1918. The staff of the monastery changed little: in 1746, it consisted of an archimandrite and 20 brethren who received salaries and bread. By 1917, there were 16 monks in the monastery. In 1757, the monastery was recognized as a priority, and governors appeared in it. From the late 18th century, archimandrites headed the Diocesan Seminary, which increased the prestige of the monastery and the educational institution.

In 1920, the monastery was closed. The transfer of its buildings began in 1996, when the abbot's and brother's corps were returned, which housed the Spiritual School. On October 6, 2005, the Holy Synod, led by Patriarch Alexy II, decided to open the Spaso-Preobrazhensky Male Monastery in Ryazan and revive monastic life. The abbot became Hieromonk Ignatius Deputatov. Now monastic life continues in the historical building alongside the Spiritual Seminary, and the churches of the monastery have been returned.