The saloon is located on the central axis of the central block, on the principal floor, on the south front, between the library and the boudoir. It is accessed directly from the hall, taking the place of Paine's intended grand staircase. The saloon is 62 feet high and has a diameter of 42 feet, taking the general form of the Pantheon in Rome, with a drum supporting a coffered dome containing an oculus. According to Hardy and Hayward, the coffered ceiling is taken from the Temple of Peace in the Basilica of Maxentius, and the niches coffered with a lozenge pattern taken from the Temple of Venus in Rome. The room was executed in 1763 as a sculpture gallery, with some of Scarsdale's casts in the niches, though these were later removed to the hall and replaced with cast-iron 'altar' stoves. The paintings of ruins are by William Hamilton, and the grisaille panels by Biagio Rebecca.

It is of interest to note the similarity between the interior decorative scheme designed by Robert and James Adam for the Edinburgh Assembly Rooms (1754-55) and the saloon at Kedleston. Adam was, perhaps, influenced by this previous work when designed this room.