Built between 298 and 306 AD, these were the greatest of the Imperial baths. The perimeter wall, enclosing a quadrangle of 14 hectares, was colonnaded along the inside and contained chambers and rooms for different uses. On the long axis of the building, Via Gaeta, marking the northern side, is where the public was admitted into the changing rooms, the gyms, and the massage rooms.

On the short axis, following the old floor plan of Trajan's Baths, stood the Basilica, the hot baths of the calidarium, the tepid baths of the tepidarium, and the swimming area. The great exedra of the baths, today's Piazza della Repubblica, was also part of the perimeter walls and was used for theatrical shows.
Over the centuries, many of the chambers of the baths were restored and used for museums, university faculties and churches.
Although the building has undergone a great number of changes, the floor plan of this enormous bath complex, purportedly built by 40,000 Christians, is still easily recognizable today.