The village of Cherkizovo, located on the way from Moscow to Tver, got its name in honor of Tsarevich Serkiz from the Golden Horde. Grand Duke Dmitry Donskoy granted him these lands in the 14th century. Later, as a result of infighting, the descendants of the Cherkizovs lost their nobility, and their estates, including Cherkizovo, became palace villages.

The first mention of the Church of the Nativity of Christ in Cherkizovo dates back to the 1580s, when the widow of Ivan the Terrible's son, who became a nun, returned the estate to the ownership of the Order of the Grand Palace. By the 1680s, the church was a wooden structure with a gabled roof, surrounded by a porch and a separate bell tower.

In 1689, the village passed into the possession of Lev Kirillovich Naryshkin, the brother of Tsarina Natalia Kirillovna. In the early 18th century, his sons Alexander and Ivan Lvovich owned the village, and then it passed to Ekaterina Ivanovna, the wife of K.G. Razumovsky. In 1738, she requested the construction of a new wooden church to replace the old one. After 30 years, the construction of a stone temple began, which was consecrated in 1790. The old church was dismantled.

The design of the temple likely belongs to an architect of the Cossack school. Initially, it was an "octagon on a square" with an apse and refectory. The facades were made in the style of early classicism. At the turn of the 18th-19th centuries, Lev Kirillovich Razumovsky actively participated in decorating the church. During the 1812 war, the church was repeatedly looted by the French.

In the 1820s, the estate belonged to Countess E.A. Uvarova. At that time, the parish had 208 households and more than 1700 people. In the 1855-1860s, chapels of the Kazan Mother of God and St. Nicholas the Wonderworker appeared in the refectory. From the second half of the 19th century, the estate was owned by Count A.S. Uvarov and his wife P.S. Uvarova. In 1913, repairs were carried out in the church.

After the revolution, despite the confiscation of valuables, services continued. The last priest was arrested and shot in 1938, and in 1940 the church was closed. During the war, the building was used as a mill, warehouse, and club. In 1991, an Orthodox community was re-established here, and services resumed in 1993.

In 1998, a restoration project was developed, aiming to restore the lost parts of the temple. In 2004-2005, the lost volumes were recreated, foundations and load-bearing structures were strengthened, and decorative elements of the facades and interiors were restored.