Ethnikon kai Kapodistriakon Panepistimion Athinon is established

The "father" of the new university was Ioannis Kapodistrias, who was the first to realize its need for the newly founded state. At the inauguration, king Otto was present and gave his name to the new academic institution naming it Ottonian University, a name that lasted until 1862. Its current name "Kapodistriakon" (Kapodistrian) was due to a condition in a large donation by benefactor Ioannis Dombolis, which was to name the institution after the first governor of Greece.

At first, its classes were taking place at the architect Kleanthis' house, and its initial students were 52, of which, very few graduated.

It included four schools: Theology, Law, Medicine, and Arts. In 1841 it was moved to the building on Panepistimiou street, which took its name for the Greek word for university, "Panepistimion." The construction of the campus of Panepistimioupolis (university-city) begun in 1960 in the suburb of Zografou. Entrance examinations for the different schools were established in 1927.