The garden was founded on October 17, 1755, by King Ferdinand VI, and installed in the Orchard of Migas Calientes, near what today is called Puerta de Hierro, on the banks of the Manzanares River.

Inside an area defined by wrought iron fencing,[1] the design by architects Francesco Sabatini and Juan de Villanueva organized the garden into three tiered terraces, arranging plants according to the method of Linnaeus.

In the 21st century it became part of a World Heritage Site, "Paseo del Prado and Buen Retiro, a landscape of Arts and Sciences".

Today's garden is divided into seven major outdoor sections and five greenhouses which allow the cultivation of species which are not suited to Madrid's Continental Mediterranean climate.

As of 2016, the online herbarium's databases contained detailed information about all the specimens in the algae, bryophyte, lichen and fungi collections.