Initially, the Leontiev parish in Yaroslavl was located in the Zemlyanoy city, near the Kirillo-Afanasevsky Monastery. In 1635, a new stone church was built on the site of the old wooden one, dedicated to St. Leontius, the bishop and miracle worker of Rostov, with an altar for the Nine Martyrs of Kizik and a bell tower above the entrance. A significant contribution to the construction was made by the Rostov merchant Vasily Fedotov Malgin. In 1688, parishioners erected a second stone church on the site of the burned wooden one, a five-domed Church of the Nativity of Christ, as well as a stone building for a charitable institution. Among the church builders stands out the name of parishioner Ivan Ivanovich Myakushkin, a Yaroslavl merchant known for his philanthropy. At the beginning of the 18th century, the parish had 61 households, and the total number of parishioners, including those living in the charitable institution, was about 200 people.

In 1778, Empress Catherine II approved a general plan for the new regular development of Yaroslavl, which significantly changed the old chaotic layout of the central part of the city. According to this plan, the area where the Leontiev parish churches were located was allocated for the construction of new state buildings. Therefore, in 1783, it was decided to abolish the parish in the Zemlyanoy city, and the church buildings were dismantled and rebuilt at the new city cemetery on the way to Uglich. The building consisted of a warm refectory with two side rooms for altars, the main church, the altar, and a bell tower 8 fathoms high. The consecration of the new church took place on May 23, 1791, the day of the discovery of the relics of St. Leontius of Rostov. The church was without a parish.

The wall paintings were completed, as stated in the church inscription, in 1806 and 1809 by contractor Semyon Stepanov Zavyazoshnikov and his apprentices Kharlampiy Petrov Dryanin and Vasily Petrov. The painting included 107 scenes in the refectory, altar, and side chapels. In 1834 and 1888, the frescoes were restored. The iconostasis was made in the 1830s by a carver from the settlement of Bolshie Soli (now the village of Nekrasovskoye), Vladimir Trubnikov.

In 1894, a literacy school for children from nearby villages and the western outskirts of the city opened at the Leontiev church. There was also a public charitable institution associated with the church, the two-story building of which was built on voluntary donations in 1846 and 1847 and has survived to this day.

In 1931, the Leontiev church was transferred to a religious community of a renovationist orientation. However, due to its small size, the community could not cover all the expenses for maintaining the building, and on December 7, 1940, the executive committee of the Yaroslavl City Council abolished the community. During the Soviet era, the interior of the church was altered (a second floor was added), and the fresco paintings were almost completely lost, except for small fragments in the altar area.

In 1991, the Leontiev cemetery church was returned to the Russian Orthodox Church, it was renovated, and burials resumed at the Leontiev cemetery.