The monastery, dedicated to the Uncreated Savior, was finally separated from the Nikol-Greek monastery, one of the oldest in Moscow, founded in the 14th century during the development of the Kitai-Gorod area, at the end of the 16th century. The first mention of the Spassky Monastery on Nikolskaya Street dates back to 1635, but it was included in the plan of Moscow drawn up by Sigismund based on descriptions from the late 16th century during the era of Boris Godunov. The monastery housed a large icon shop, which determined its name Zaikonospassky. In the 1660s, significant work on the improvement of the monastery was carried out with the funds of the boyar and voivode F. Volkonsky.

In 1665, the well-known educator and encyclopedist of the 17th century, Simeon (Polotsky), became the abbot of the monastery, who founded a school for clerks of Moscow orders there. In 1680, he was succeeded by his student Silvester (Medvedev), who composed the first charter of the Slavonic-Greek-Latin Academy under Tsar Fyodor Alexeyevich. However, due to the early death of the tsar and the subsequent "Streltsy turmoil," the academy was opened only in 1685, initially in the neighboring Bogoyavlensky Monastery.

The founders of the academy were Greek monks, brothers Joachim and Sophronius Likhudy, graduates of the Padua Academy. The academy's program included a wide range of humanities and natural sciences, and its most famous student was M.V. Lomonosov. With the emergence of new centers of secular education under Peter I, the Zaikonospassky Academy gradually became the center of higher ecclesiastical education. It remained in the monastery until 1814, when it was transferred to the Trinity-Sergius Lavra and transformed into the Spiritual Synodal Academy.

The modern architectural complex of the monastery mainly dates back to the late 17th and the first third of the 18th centuries. In the mid-1680s, with the funds of the Greek hierodeacon Miletiy, work was carried out to accommodate the academy. At this time, the structure of the monastery acquired a regular character, with buildings forming a ceremonial square in front of the cathedral from the 1660s.

With the granting of state status to the academy in 1701, the renovation of the cathedral began, which continued until the 1730s with the participation of architects I. Zarudny and I. Michurin. The new cathedral became an outstanding architectural monument of Moscow from the first third of the 18th century. It is located on the ridge of Kitai-Gorod, towards the Neglinnaya River, and still completes the panoramas from Zaneglimenya. The cathedral stands on a high pedestal and has an original structural and artistic solution characteristic of the architecture of Moscow at that time.

In the early 20th century, the building of the Nikolsky trading rows was constructed on Nikolskaya Street according to the design of L.N. Kekushev, one of the best buildings in Moscow from the Art Nouveau era. The facade of the building is decorated with stucco decoration featuring floral garlands and griffin figures.

The Zaikonospassky Monastery was closed in 1929 and resumed as a Patriarchal courtyard in 1992. The ensemble underwent restoration in preparation for the cultural program of the 1980 Olympics. Restoration work was carried out in the cathedral during the organization of the parish in 1991.