Designed by the architect Carlo Maciachini (1818–1899), it was planned to consolidate a number of small cemeteries that used to be scattered around the city into a single location.

Officially opened in 1866, it has since then been filled with a wide range of contemporary and classical Italian sculptures as well as Greek temples, elaborate obelisks, and other original works such as a scaled-down version of the Trajan's Column.

The main entrance is through the large Famedio, a massive Hall of Fame-like Neo-Medieval style building made of marble and stone that contains the tombs of some of the city's and the country's most honored citizens, including that of novelist Alessandro Manzoni.

The memorial of about 800 Milanese killed in Nazi concentration camps is located in the center and is the work of the group BBPR, formed by leading exponents of Italian rationalist architecture that included Gianluigi Banfi.

There are also family shrines, two of which were designed by Maciachini, columbaria, and ossuaries along the northern and western cemetery walls and burials in the central building.

There are many monuments of artistic value built by important architects and sculptors, described in the guide book by Giovanna Ginex and Ornella Selvafolta .