Frankfurt's Historical Museum had an Archaeological Department from the end of the 19th Century, with collections of old indigenous and Classical artefacts. Divergence of responsibilities and lack of space led to the foundation of a separate Museum für heimische Vor- und Frühgeschichte (Museum of Indigenous Pre- and Early History) in 1937.

Its first domicile was the old Dominikanerkloster, in which the numerous roman stone funerary monuments could be made accessible to the public. The war forced the Museum to close as early as 1942 and destroyed part of the collection. Its new Director, Ulrich Fischer, was able to reopen the 'Museum für Vor- und Frühgeschichte' in 1954, in the Holzhausenschlösschen building with a permanent exhibition about Frankfurt's archaeology.

In the following two decades, the wideranging and laborious large-scale excavations – in Roman NIDA (Heddernheim), in Frankfurt's historic centre and in the city's woodlands – were at the centre of the museum's work. The unusual quantity of objects retrieved soon burst the museum's storage capacity. Two further permanent exhibitions had to be housed away from the building: the exhibition about the Roman city of NIDA,in 1976, in the Deutschordenshaus and in 1977 the exhibition on the excavations in the historic city centre, in the Historical Museum.

Since 1969, the museum has been housed in the Gothic Karmeliterkirche – which was rebuilt by Josef Paul Kleihues – and in the newly-built adjoining wings (approx. 1400 m² of exhibition space). Further Roman stone monuments (lapidarium) are displayed in the southern section of the monastery's cloister.

The Museum, furthermore, presents the results of its extensive excavations in the Jewish ghetto at Börneplatz together with the restored foundations of houses in the Museum Judengasse, an annexe of the Jüdisches Museum (Jewish Museum).

Since 2002 it has been called the Archäologisches Museum.