The main church of Ufa today inherited its high status from the Resurrection Cathedral, which was also revived and retained its cathedral significance. Planning for the construction of the Church of the Nativity of the Virgin began in the late 19th century, as confirmed by preserved drawings. The site for the church was chosen by Bishop Anthony of Ufa. The construction was long and costly, and, as usual, funds were lacking. Only in 1901 was the ceremony of laying the church held, after which the main work began thanks to the help of merchant Nikifor Patokin, who allocated funds for the construction of the building and the bell tower, purchasing bells for it. The church was planned to be located on the eastern side of Priyutskaya Street, named after the children's shelter opened in 1849. The street flowed into the city square surrounding the future cathedral.

Despite the patron's support, the construction of the cathedral was completed only in 1909. The stonemasons used technologies tested during the construction of the Nikolskaya Church. The Christmas temple was distinguished by its green roof and bronze crosses. The bell tower was decorated with a three-tiered structure, and the wooden dome was sheathed in iron and painted to resemble brick. On August 23, the bells were raised to the bell tower, the largest of which weighed 50 poods and 35 pounds. The church was ready to receive parishioners, its length was 206.5 fathoms, and its width was 10.5 fathoms.

On September 6, 1909, the cathedral was consecrated by Bishop Nafanail. The northern chapel was consecrated in the name of St. Nicholas the Wonderworker, and the southern, in the name of Archangel Michael. The first rector was Priest Vasily Lezenkov. By 1916, the parish numbered 1,747 people, but the church had no land holdings, and the priests did not receive a salary. The cathedral became the last Orthodox church in Ufa built before the revolution. In 1919, it housed a hospital, but church life continued.

During the Soviet era, the church was closed, and its property was looted. In 1934, the building was transferred to a medical institute, but it remained empty until 1935 when it was handed over to 'Bashkino'. In 1936, the NKVD staff were placed in the church, and in 1938 it was used as a warehouse. During the Great Patriotic War, aircraft workshops operated in the building. After the war, the building was handed over to the 'Yondoz' cinema, but it was heavily remodeled beforehand.

In 1991, after numerous appeals from believers, the building was returned to the Russian Orthodox Church. Reconstruction began, restoring the dome and bell tower. In 1992, the church became known throughout Russia due to the myrrh-streaming icons. In 2016, Patriarch Kirill granted the church the status of a cathedral.