The neoclassical building that has housed the Historical Museum of Crete since 1953 was erected in 1903 by Andreas L. Kalokairinos, to a design by K. Tsantirakis, on the footprint of an earlier house built in 1870 by Minos Kalokairinos—merchant, antiquarian, and the first excavator of Knossos—under the supervision of the architect L. Kavantzoglou and a specialist engineer summoned from Smyrna. The previous building, which had itself replaced the Krassadakis residence destroyed by the earthquake of 1856, was set on fire and ruined during the events of 25 August 1898.

The present structure is listed as a historic preserved monument. It is a two-storey stone building with a raised ground floor. The original entrance (today on Lysimachou Kalokairinou Street) is articulated by a marble portico with two Doric columns of white Pentelic marble. Above, the portico roof forms a small balcony with an openwork marble parapet, a copy of that on the Karapanos house on Stadiou Street in Athens; this marble composition is the work of the sculptor K. Perivoliotis. On the main façade, the ground-floor openings, as well as those in the southern section of the east and west elevations, are arched windows framed by  female figures supporting a pediment, while the remaining openings have simple straight frames. On the south side of the building, an enclosed courtyard is formed with a perimeter wall; the wrought-iron railings and the gate are the work of Thomas Tsokopoulos.

Inside, wall paintings with vegetal motifs decorate the ceilings of the rooms, while the corridor ceiling is embellished with painted imitation coffering, and its wall terminations feature scenes from the Iliad and the Odyssey. These decorations are the work of craftsmen employed by the decorator Antonis Stefanopoulos.

In 1953 the building was renovated to serve as a museum, to plans by the engineers I. Tzobanakis and K. Lasithiotakis. In 1961 a new three-storey wing was added, designed by Patroklos Karantinos; between 1988 and 1997 this wing underwent substantial additions—reworking of the exterior and a new internal layout—according to designs by the architect Giannis Pertselakis.