The first mention of the Intercession Church is found in the "Watch Book" of Grigory Kireevsky from 1615: "The settlement of the White Cossacks and atamans, and in the settlement a church in the name of the Intercession of the Holy Virgin, wooden, with a porch, and in the church icons and bells and all church buildings of the parishioners." The term "new" was not applied to it, which allows us to date its appearance to the beginning of the 17th century.

In 1700, Saint Mitrophan, the first bishop of Voronezh, issued a blessed decree for the construction of a new church, as the old wooden church had fallen into disrepair. In 1736, the construction of a stone church began.

In 1748, an altar in the name of the Meeting of the Lord was consecrated. At the end of the 18th century, a second altar in the name of the icon of the Mother of God "Sign" appeared in the church, consecrated on February 11, 1796, by Bishop Mephodiy of Voronezh and Cherkassy (Smirnov, †1799). In 1791, a three-tiered bell tower was built. The largest bell, brought from Moscow, weighed 181 poods and 5 pounds (about three tons).

The need to rebuild the main church became evident. Major works were completed in 1835, but finishing continued until 1841. The church was consecrated on July 14, 1841, by Saint Anthony, Archbishop of Voronezh and Zadonsk. The Ionic portico and the wide drum of the main nave give the church a majestic appearance.

In 1847 and 1848, warm altars in the name of the Meeting of the Lord and the icon of the Mother of God "Sign" were consecrated, arranged in the refectory by merchant S.P. Yefimov and with the efforts of the parishioners.

During repairs in 1872, church elder V.O. Ukhin updated both altars in the refectory, and the iconostases of the main church and altars were covered with red gold.

Architecturally interesting is the house of the priests, built next to the church according to a standard project in the early 19th century. The churchyard contained a cemetery where priests and elders were buried.

By 1904, there were 1,282 parishioners in the Intercession Church. The church staff included two priests, one deacon, and two psalmists.

Services were held until 1932. After its closure, it housed a Defense House and then an anti-religious museum. A Foucault pendulum was installed under the dome.

In August 1945, a group of believers, led by M.P. Vdovin and F.T. Khrenov, began to petition for the return of the church. They were supported twice by Patriarch Alexy I (Simansky, †1970). On March 2, 1948, the Council for the Affairs of the Russian Orthodox Church decided to satisfy the believers' request to reopen the Intercession Church in Voronezh and proposed to register the community, transferring the building and property to it. In May 1948, the building was handed over to the Orthodox community.

In 1948, under Bishop Joseph (Orekhov), the episcopal see was transferred from the Nikolsky Church to the Intercession Church, which became the cathedral of Voronezh.

On November 14-15, 1998, the first visit of the Primate of the Russian Orthodox Church to the Voronezh Diocese took place. Patriarch Alexy II held a moleben at the relics of Saint Mitrophan, an all-night vigil, and the Divine Liturgy in the Intercession Cathedral.

The cathedral hosts a Sunday school, a parish library, social and catechetical departments. Since December 2009, a pilgrimage department of the Voronezh and Borisoglebsk Diocese has been operating here under the guidance of Archpriest Sergey Mozdor.