One of the oldest cemeteries in Moscow, recognized as a cultural heritage site, was founded in 1771 near the Danilov Monastery, next to the settlement of Danilovskaya Sloboda. Its establishment is linked to a plague epidemic when the number of deceased was so high that there were not enough burial places in the city. The Senate prohibited burying the victims of the disease within the city limits.

During the epidemic, up to eight hundred people were buried daily at the cemetery. On the slope of the Andreevsky ravine, near the central part of the cemetery, a section was designated for deceased foreigners and non-Orthodox individuals. This is now the Muslim section of the cemetery with a separate entrance. Here lies the grave of the famous dancer and choreographer Mahmud Esambaev.

Before the revolutions of the early 20th century, Danilov Cemetery mainly served as a burial site for merchants, craftsmen, and townsfolk from the nearby sloboda. One of the most famous merchant burials belongs to the Tretyakov family, known thanks to Pavel Mikhailovich, the founder of the Tretyakov Gallery. The family burial site of the Botkin family is also located here.

In 1916, Moscow writer and local historian Alexei Saladin noted that Danilov Cemetery could be called merchant, as it is located near the merchant district of Zamoskvorechye. The cemetery had many merchant monuments typical of the mid-20th century, but today most of them have been lost.

Notable individuals buried at Danilov Cemetery include historian Ivan Kovalchenko, linguist Afanasy Selishchev, philologist Sergey Averintsev, art historian Sergey Durylin, Moscow expert Mikhail Alexandrovsky, football player Valery Voronin, writer Yuri Yakovlev, actor Boris Novikov, journalists Yaroslav Golovanov and Vladimir Kara-Murza, economists Alexander Livshits and Nikolai Shmelev, and film scholar Gleb Skorokhodov.

The cemetery is also the final resting place of Heroes of the Soviet Union Nikolai Sidorov, Ivan Zaykin, and Ilya Kotov. During the Soviet era, the cemetery became the burial site for many representatives of the Orthodox clergy.

The central cemetery was known for the grave of Saint Matrona Dmitrievna Nikonova. In 1998, her relics were transferred to the Pokrovsky Monastery, but the flow of pilgrims did not diminish.

Many members of the merchant dynasty of the Tretyakovs are buried at Danilov Cemetery. In 2021, the restoration of four gravestones recognized as cultural heritage sites was completed. The gravestones of Zinaida and Sofia, the wife and daughter of Sergey Vasilyevich Tretyakov, as well as the gravestones of four cousins of Pavel and Sergey Mikhailovich Tretyakov, were restored.

A snow-white church in the Empire style with a bell tower, where services for the deceased are held, was built on the site of a wooden church in honor of the Holy Martyrs of Chersonesus, erected at the end of 1772. By 1828, the church had fallen into disrepair, and merchant Semyon Lepeshkin initiated the construction of a new one, next to which a charitable institution was established. He also funded the construction of the cemetery fence and a wing. The new church was consecrated in 1838 in the name of the Descent of the Holy Spirit, designed by Fyodor Shestakov. In 1901, a church dedicated to St. Nicholas the Wonderworker and a chapel were built on the cemetery grounds according to the design of Nikolai Strukov. The old iconostasis and frescoes from 1832 have been preserved.

During the war, an anti-aircraft battery was located on the cemetery grounds, and concrete pillboxes were installed, two of which have survived to this day.

The total area of the cemetery is 35 hectares.