The Moscow hospital, now known as the Main Military Clinical Hospital named after N.N. Burdenko, was founded in Lefortovo by Peter I's decree in 1706. At that time, the first medical-surgical school in Russia was opened at the hospital, led by Peter I's personal physician, Nicholas Bidloo, a graduate of Leiden University.

Initially, the hospital consisted of a single stone building in Dutch style with the Church of the Resurrection of Christ and thirty wooden structures on the banks of the Yauza River. Among them were an anatomical theater, an alchemist's chamber, a pharmacy, and facilities for students and patients. Nearby was a botanical garden with medicinal plants. The main building was adorned with an octagonal wooden dome topped with a carved gilded statue of Mercy. During the Peter the Great era, the hospital even had a theater where students of the Medical-Surgical School staged the first Russian plays and intermezzos.

By the end of the 1750s, architect D. Ukhtomsky reconstructed and expanded the complex, adding a two-story stone building for the church department. In May 1756, a department for the mentally ill opened in this building, the first of its kind in Russia.

Under Catherine II, the hospital fell into decline. In 1763, a fire destroyed the right half of the main building and the church. The buildings were in such poor condition that in 1764, there were plans to dismantle them and relocate the hospital. However, the hospital staff managed to keep it in its original location.

Under Paul I, a project for new stone buildings was approved, developed by Moscow architect I. Egotov. In 1797 and 1802, the main building of the hospital was constructed, which has retained its appearance to this day. In November 1801, the altar of the oldest church in the hospital was consecrated in the name of the apostles Peter and Paul.

The hospital represents an ensemble of the Empire style, one of the few that survived the Moscow fire of 1812. Some of the wooden buildings were restored in stone in 1818 and 1830. A brick chapel for the burial of the deceased was also rebuilt, which has survived to this day.

In 1823, Alexander I, upon visiting the hospital, ordered the buildings to be connected by passageways, increasing the number of beds to 1800. After that, the architectural appearance of the hospital changed little, except after the Russo-Turkish War of 1877-1878, when an additional church altar was consecrated in the main building in honor of the Mother of God of All Who Sorrow. In 1917, one of the hospital's departments was moved to the church.

In 1946, the hospital was named after academician N.N. Burdenko, the founder of domestic neurosurgery. During the construction of new buildings in the 1930s and 1990s, the classical ensemble was preserved. All buildings from the 18th-19th centuries are recognized as cultural heritage sites of federal significance.