The department was established as the Institut für Völkerkunde in 1946, when the Johannes Gutenberg University reopened after World War II. From 1947 to 1956, the department was headed by Adolf Friedrich. From 1951 to 1954, his assistant, Erika Sulzmann, led one of the first German anthropological research journeys after World War II and conducted fieldwork on the Ekonda and Bolia in Belgian Congo (now Democratic Republic of the Congo). Erika Sulzmann established the department's library and ethnographic collection. Furthermore, she ensured the continuity of research on Africa during the following years, when the department was confronted with a comparatively quick succession of professors. In 1957, after Friedrich had passed away in 1956, Wilhelm Emil Mühlmann – who had been holding an adjunct professorship ("Diätenprofessur") for Sociology and Ethnopsychology ("Völkerpsychologie") at the department since 1950 – took over as Head of the Department.
In 1960, Mühlmann left the department to take up a professorship in Heidelberg. His successor was Karl Jettmar, whose regional research focused on Asia. In 1964, three years after his appointment, Jettmar followed Mühlemann to Heidelberg. Only afterwards, a strong regional focus on Africa was eventually established at the department. In 1965, Eike Haberland became Head of the Department. Three years later, in 1968, Haberland took over the Chair of Cultural Anthropology as well as the directorship of the Frobenius Institute at the University of Frankfurt am Main. In 1969, Ernst Wilhelm Müller was offered the Chair of Anthrpopology in Mainz and became Head of the Deparment. As a student research assistant, Müller had participated in Erika Sulzmann’s Congo journey. Supervised by Mühlmann, he had acquired his habilitation at the University of Heidelberg, In the same year, a new Chair of African Culture and Society – converted from the university's former Chair of Comparative Cultural Studies – was established at the department. In 1974, Gerhard Grohs, a sociologist, was appointed the first holder of this Chair. Grohs pursued the sociological orientation of the department initiated by Mühlmann. In 1997, after Groh's retirement, Thomas Bierschenk became his successor and renamed the Chair as "Chair of African Cultures and Societies".
After Mülller's appointment, the department was called Department of Anthropology ("Institut für Ethnologie"). In 1975, it was renamed Department of Anthropology and African Studies to highlight the fact that the department also comprised a second discipline, namely African Languages and Linguistics (formerly African Philology). A third Chair was created at the department in 1984, to which Ivo Strecker was appointed. Karl-Heinz Kohl succeeded Müller in 1987. When Kohl moved to the Department of Historical Anthropology and the Frobenius Institute in Frankfurt in 1996, his position was temporarily filled until Carola Lentz became his successor in 2002. She held this "Chair of Anthropology" until she retired in 2019, after which the position was turned into a junior professorship with tenure track.
Ivo Strecker’s professorship was transformed after his retirement into a "Chair of Anthropology and African Popular Culture", which has been held by Matthias Krings since 2005. In 2016, Heike Drotbohm was appointed to a Heisenberg Professorship in Anthropology with a focus on African Diaspora and Transnationalism; in 2019, she succeeded Thomas Bierschenk after his retirement. The newly created "Chair of Anthropology with a focus on Aesthetics" was filled in 2017 with Markus Verne.