Isaias Afwerki was born in 1946 in the Aba Sha’ul district in Asmara, Eritrea, then part of Ethiopia, to parents Afwerki Abraha and Adanesh Berhe. His father, Ato Afwerki, a native of Tselot village, just outside Asmara, was a low-ranking official working at a state-owned company, Tobacco Monopoly, his mother is Woizero Adanesh. Afwerki hails from the Biher-Tigrinya ethnic group.
Isaias grew up in Asmara and graduated from Prince Makonnen High School (PMSS) in 1965 scoring high in the General School Leaving Certificate Exams, thus he was able to be admitted to the highly competitive College of Engineering at Haile Selassie I University (now called Addis Ababa University) in Addis Ababa, Ethiopia. However, a year later in September 1966, he decided to join the forces engaged in the Eritrean Armed Struggle for Independence.
Isaias is married to Saba Haile and has two sons and one daughter.