In 1770, a spiritual men's school known as a seminary was opened in Saratov, which was part of the Astrakhan Diocese. However, by early 1777, after a new seminary was opened in Astrakhan, the Saratov school was closed, and the issue of spiritual education in the city was forgotten for a long time, despite numerous attempts to revive it. The establishment of the Saratov Diocese in 1799, centered in Penza, did not change the situation.

Only in 1820 was an initial spiritual school founded in Saratov, and in 1830, the seminary finally opened. The solemn opening took place on October 26 (November 7) in the Trinity Cathedral; after a prayer service, participants walked in a procession to the neighboring building, which had been acquired for the seminary by the Holy Synod a year earlier. Classes were also held in another mansion, which housed the seminary's dormitory.

In the 1870s, a decision was made to construct a new building, the project of which was developed by architect N. N. Markov. Construction began in 1882 and was completed in 1885. In the same year, Bishop Pavel consecrated the seminary's chapel. The lower floor of the new building contained the apartments of the rector and teachers, a library, and other rooms. The mezzanine housed classrooms and the chapel, while the upper floor had bedrooms and washrooms. In 1894, a bell tower was built in the courtyard, and in 1899, the Society for Assisting Underprivileged Students of the Seminary was established.

During the First Russian Revolution in 1906, the seminary students participated in protests against the Military Court's decision. These events led to reforms in the seminary initiated by Bishop Germogen. During World War I, the seminary building was used for military needs.

With the Bolsheviks coming to power in 1918, the seminary was closed, and its building was handed over to a military organization and party courses. Later, it housed a pedagogical institute. The seminary was revived only in 1947 and relocated to a new building.

The historic building on Michurina Street was returned to the seminary in 2007 thanks to the efforts of Bishop Longin. After extensive renovations, the building was fully restored by 2014. Today, the seminary offers full-time and part-time education, has a library, and publishes an annual collection of works. Pilgrimages are organized for students, and the faculty includes both clergy and laypeople.

Among the notable alumni of the seminary are philosopher and revolutionary N. G. Chernyshevsky, as well as other distinguished figures such as orientalist G. S. Sablukov and metropolitans Juvenaly, Ioann, Serafim, and others.