The foundation of the Church of the Three Saints is closely linked to the establishment of the Taurida Spiritual Seminary in Simferopol. Initially, Bishop Alexy Rzhanitsin appealed to the Holy Synod with a request to open the seminary, but due to financial difficulties, the project was not realized. Later, Archbishop Guriy Karpov, now canonized, submitted the necessary documents to the Synod, which decided to open the seminary gradually over six years, starting in 1870. On May 30, 1869, Emperor Alexander II granted permission for its opening. Construction of the building began on April 11, 1871, based on the design of architect K.N. Yeremeev and engineer V.A. Grachev, with contractor N.A. Masyakhin overseeing the work.

Over time, the need arose for the construction of a separate seminary church. On July 18, 1900, in honor of the seminary's 25th anniversary, the church was laid. Architect A.I. Karapetov presented the project and estimate, while merchant Nikolai Solovyov took charge of the construction. Work began in February 1901 and was completed in September 1903. The church was consecrated on September 11, 1903.

That same year, inspector R. Sokolov described the church, noting its tall and beautiful architecture in the style of ancient Christian basilicas. The altar was elevated and enclosed by an oak iconostasis made at the Zheverzhev factory. The central part of the church was adorned with an arch supporting the dome and divided into two naves. The frescoes were executed by artist Dmitry Petrovich Pravednikov.

After the revolution, in November 1920, the Taurida Spiritual Seminary was closed, and in 1922, the church was also closed. In the 1920s, the church lost its domes, frescoes, and iconostasis, and the bell tower was destroyed. For a long time, the building was used for purposes other than its intended use, in recent years as an archive.

In 1989, the church was returned to the Simferopol and Crimean diocese, and services resumed here. On April 2, 1989, Archbishop Varlaam consecrated the church, and it once again became a place of prayer.

In 1990, Priest Georgiy Severin was appointed as the rector. In 1997, with the return of the Taurida Seminary and the establishment of a pastoral spiritual school based on it, the church once again became a place of prayer for teachers and students.

Since 2007, the church was restored to its seminary status, and active restoration began in 2008.