In the early 1950's, Alexander Schenk Graf von Stauffenberg, chair of ancient history at the LMU of Munich, campaigned among West German ancient historians for the establishment of an institute for epigraphy and historical geography. In view of the consolidating stalemate of Germany's division and the retaining of the traditional epigraphic academy in East Berlin, Stauffenberg was concerned with securing the future of  elementary epigraphic research in West Germany. The Kommission für Alte Geschichte und Epigraphik was subsequently founded in 1952 at the conference of the Mommsen Gesellschaft in Marburg and was added to the register of associations in Munich in 1953.  The commission initially consisted of seven, then nine professors appointed by habilitated ancient historians of Germany in the manner of DFG (Deutsche Forschungsgemeinschaft)  expert reviewer elections. Stauffenberg became founding chairman, whereas the commission's operational manager and  initially sole employee was its so-called assistant, firtst Hermann Bengtson, then Robert Werner, Hans Kaletsch, and eventually Edmund Buchner. The  commission's first meeting took place in Würzburg from 29 to 30 May 1953. Almost right from the beginning cooperation with the DAI was close. Its president belonged ex officio to the commission, which in turn sent a member to the  DAI's central directorate. The commission's first major research programme took shape with the series Staatsverträge des Altertums which was prepared by commissioned external editors. Stauffenberg's successor was Hans Schaefer (Heidelberg, 1957-1959), who founded the series Vestigia. He again was succeeded by Helmut Berve (Erlangen, 1960-1967). A specialised academic curriculum was created in 1961, and intended to supplement university modules in elementary level disciplines of the classical studies. This curriculum which  was interrupted only once under the pandemic in 2020, has been held annually ever since and become a permanent institution.

Edmund Bucher initiated the commission's affiliation process to the DAI in 1967 and oversaw its finalisation in 1969 with his nomination of the commission's first full-time director. Its integration to the DAI enabled the commission to further develop into a resourceful research body. Together with Michael Wörrle, Buchner masterminded the commission's transfer into  today's premises in Munich's Amalienstraße where he founded the journal Chiron in 1970. The commission received  international acclaim after its management of the VI International Congress of Greek and Latin Epigraphy held in Munich in 1972.  When Buchner was appointed president of the DAI in 1979, his deputy Michael Wörrle succeeded him as first director at the commission and continued the expansion of research activities. Wörrle himself was   involved  particularly with the study of the epigraphy in Asia Minor.  Under the guidance of Armin Stylow the commission furthermore asserted itself through the new edition of the Latin inscriptions from the Iberian Peninsula within the framework of the Corpus Inscriptionum Latinarum (CIL II²). This led to the creation of the Centro CIL dos at the Universidad de Alcalá de Henares. Türkiye  and Spain still are the geographical focus of the commission's work programme and are sustained through particularly close links with the DAI departments in Istanbul and Madrid. The largest project of the commission in numismatics was the supervision of the edition of the Sylloge Nummorum Graecorum Deutschland by Hans-Roland Baldus. Under the second director, Dieter Hennig, the library was enlarged to become one of the most important international institutions in the fields of epigraphy, numismatics, and papyrology. Christof Schuler and Rudolf Haensch, became the  two new directors of the commission in 2004.

While Schuler continued epigraphic fieldwork in Türkiye, Haensch developed the commission's activities through the  Corpus der Urkunden der römischen Herrschaft (CURH), principally within the field of papyrology. New forms of collaborative research strengthened the  commission's networking inside the DAI  since 2006 through its participation in the implementation of several DAI research clusters, and since 2009 through work at the Münchner Zentrum für Antike Welten (MZAW). Schuler served as spokesperson of the MZAW between 2017 and 2020 and, as part of an excellence initiative, was the founding member and principal investigator at the graduate school Ferne Welten (2012-2020) at the LMU. Cooperation with the LMU was further deepened through the setting up of a junior professorship for papyrology by joint appointment of the DAI and the LMU. The chair is currently held  by Matthias Stern for a period of three years as from 2021. As for the DAI, this has been the first such procedure ever. Cooperation with other universities also has also become a major asset for the   commission's work. In addition to the various partners in Spain and Türkiye, one may also count the Westfälische Wilhelms-Universität at Münster, with which the commission has been cooperating since 2021 in the DFG project Corpus der Inschriften von Patara, and the Université Bordeaux Montaigne, where the GymnAsia project  funded by the DFG-ANR and covering the history of ancient gymnasia in Southern Asia Minor too has been running since 2021.