In the summer of 1619, Cossacks from Tobolsk, led by Maxim Trubchaninov, ventured into the lands of the Tungus, where they established the Tungus fort. This first Russian settlement on the Yenisei, built by Trubchaninov's Cossacks, was initially called Tungusky, then Kuznetsky, and only later received the name Yenisei fort.

The settlement was built on the left bank of the Yenisei, on a hill near the mouth of the Kema River. By the 1620s, it began to expand, attracting "traders and wandering people," and gradually descended from the hill. Yeniseisk quickly became a trading and administrative center for a vast region, from which new parties of land explorers set out. Yenisei Cossacks founded cities such as Krasnoyarsk, Yakutsk, Irkutsk, and Nerchinsk. Among them was Semyon Dezhnev. The town became not only a political but also a spiritual center of the region. In 1642, on a high green hill half a kilometer from the town, the Spaso-Preobrazhensky Monastery was founded.

According to legend, a hermit, monk Timofey Ivanov, settled in these places as early as 1592, around whom a small monastic community gathered. In 1642, the monastery was not founded but merely received "approval from the higher authorities" from the Tobolsk Archbishop Gerasim.

The Yenisei Monastery remained sparsely populated and poor for a long time; its lands, mills, fishing, and saltworks did not bring in significant income. All the monastery's buildings remained wooden for over a hundred years, and only in the 1730s did stone construction begin.

The first stone structure of the monastery was the Spassky Cathedral, built in the Siberian Baroque style and consecrated in the 1750s. Later, the Ilyinsky chapel, the warm Pokrovskaya church, and the bell tower were added. The construction of the cathedral involved the master of the Uspensky Dalmatov Monastery, Ioakinf Denisov, sent by the Tobolsk metropolitan to train local craftsmen. The Spassky Cathedral was designed for the small monastic brotherhood. Its carved gilded iconostases have not survived. The massive octagonal bell tower adjoins the cathedral. It housed the monastery's main relic, the icon of "The Savior Not Made by Hands."

In the 1780-1800s, stone Holy Gates with the church of Zacharias and Elizabeth were built at the monastery, along with part of the fence and the abbot's residence. The church of Zacharias and Elizabeth, erected between 1785 and 1790 and consecrated in 1822, was one of the main verticals of Yeniseisk. In 1859-1860, new iconostases were installed in the church, funded by merchant A.S. Balandin. The monastery was surrounded by a fence 590 meters long, partly stone and partly wooden. In one of the monastery's cells, and later in a local hospital, Decembrist N.S. Bobrishchev-Pushkin spent three years in confinement.

For a long time, the Spassky Monastery was an important missionary and educational center. Since 1780, it had a "school for all classes," later transformed into a parish school.

During the Soviet era, the monastery suffered greatly: the interiors of the churches were destroyed, part of the buildings were ruined, and the surviving ones were severely damaged.

The revival of the monastery began in 1990. Despite the local authorities' reluctance to assist in the restoration, on December 6, 1990, Bishop Antoniy of Krasnoyarsk and Yenisei conducted the first archpastoral service in the newly opened monastery.

Documents sent by Bishop Antoniy to secular authorities overseeing the restoration testify to the difficulties of the monastery's revival: "The building, which has not attracted your attention for decades and is losing its architectural appearance, has been received by the monastery in a barbarically mutilated state. Imposing fines for this barbarism makes no sense, just as it does to hinder the monastery from adapting it for life."

Since 1990, the duties of the abbot were performed by Hieromonk Mephodiy Yesin. By the decree of Patriarch Alexiy of Moscow and All Russia on August 3, 1992, he was appointed the abbot of the revived monastery with elevation to the rank of igumen. Father Mephodiy passed away on October 3, 2005, after a severe illness.

By the decision of the Holy Synod on October 6, 2008, Igumen Nikanor Anfilatov was appointed as the abbot of the monastery. By the decision of July 13, 2015, Bishop Nikanor of Yeniseisk and Lesosibirsk became the archimandrite of the monastery.

Until 2009, services were held in the Preobrazhensky chapel, which was attached to the Spassky Cathedral. Currently, after the restoration of the main temple, three altars have been consecrated: in the name of the Merciful Savior, in honor of the Beheading of St. John the Baptist, and in the name of the Prophet Elijah.