Verkhoturye became the center of Orthodoxy in the Urals and Siberia thanks to the Holy Nikolaevsky Monastery, which became the first Orthodox monastery beyond the European part of Russia. Although the Trinity Cathedral was contemporaneous with the city, the monastery was founded a little later, in 1604. This happened after Hieromonk Ion from Poshekhonye appealed to Boris Godunov with a request to establish a monastic community in the new city. Moscow granted permission, but due to a lack of funds, construction was delayed, and Ion had to personally go to the tsar for support. Eventually, a small wooden church was built, consecrated in honor of Saint Nicholas of Myra, along with several cells. The monastery lived a quiet prayerful life, but almost nothing is known about its first century due to fires that destroyed the archives. It can be assumed that the community developed alongside the city, for which the 17th century became a 'golden' age. An important event in the history of the monastery occurred a hundred years after its founding.

In the early 18th century, the monastery gained its patron saint, who lived in the world but became the heavenly protector of the Urals after his death. The relics of the righteous Simeon of Verkhoturye were transferred to the monastery from Merkushino in 1704 and became its main shrine, attracting many pilgrims. In 1716 and 1762, the monastery suffered from fires, but the reliquary with Simeon's relics remained unharmed. By the early 20th century, the number of pilgrims increased so much that the small cathedral could not accommodate them. After the celebration of the monastery's 300th anniversary and the 200th anniversary of the transfer of the relics in 1905, a huge Exaltation of the Holy Cross Cathedral was laid, becoming the third largest in Russia. The consecration of the cathedral took place in 1913, and the relics of Simeon were transferred there. However, soon the revolution began, and with the arrival of Soviet power, the monastery was occupied by Red Army soldiers, and the monks were sent to dig trenches.

The difficult times gave rise to many new martyrs, including the executed hieromonks Iakinf, Kallistos, and Apollinarius, who were canonized in the 1990s. In 1925, the monastery was closed and turned into a colony for minors. In 1929, Simeon's relics were transferred to the Tagil Museum of Antireligious Work, where they became an object of atheistic propaganda, but people continued to pray before them. In 1935, the relics were transferred to the Ural Antireligious Museum. After the disbandment of the museum's funds in 1946, the relics were transferred to the Regional Local History Museum. Only in 1989 were they returned to the Russian Orthodox Church and placed in the Church of the All-Merciful Savior, and in 1992, they were transferred to the restored Exaltation of the Holy Cross Cathedral in Verkhoturye.

Today, the monastery is fully restored, and the number of pilgrims continues to grow, returning Verkhoturye to its status as the spiritual center of the Urals. The Nikolsky Cathedral was dismantled in 1936, and with the revival of monastic life, the question of its restoration arose. It was decided to build a small Nikolsky Church with elements of the architecture of the former cathedral. This church, consecrated in 2004, became a decoration of the monastery.

The Exaltation of the Holy Cross Cathedral, built in the Neo-Byzantine style, impresses with its size but creates a sense of lightness and brightness inside. It has become the architectural dominant of the monastery. Under the shade of the cathedral rest the relics of the righteous Simeon of Verkhoturye, and nearby lies a book in which pilgrims record their stories of help from the saint, especially many names of children born through the prayers of Simeon.