[3][1] The university was founded as the "Catholic College of Santa Famiglia" in 1958 by the "Piae Madres Nigritiae" (Comboni Sisters).

The roots of the university are connected to the 1940s when Dr. Vincenzo Di Meglio [it] promoted the creation of the "School of Medicine" in Italian Asmara.

It is also linked historically to the Istituto Italiano Statale Omnicomprensivo di Asmara.

New courses, staff, day and evening extension programs and campus buildings revived the university, together with a bilateral agreement to exchange students and faculty with the University of Addis Ababa, particularly focusing on graduate training in Addis Ababa to produce faculty for Eritrea.

[6] In 2001, students protested against the Ministry of Education's call for them to take leave during the rainy seasons, and to temporarily retrain as census workers in rural Eritrea.

After the final closure of admission in 2003, seven higher education institutions inherited the accreditations of the University of Asmara.