Tsafendas was born in Lourenço Marques (today's Maputo) to Michalis Tsafandakis (Μιχαήλ Τσαφαντάκης, also spelled Miguel Tsafandakis), a Greek marine engineer from Kitharida, a small village near Heraklion, Crete, and Amelia Williams, a Mozambican woman of mixed race. He was sent to Egypt when he was three to live with his grandmother and his aunt. He returned to Mozambique four years later; then, at the age of ten, moved to Transvaal, where he attended Middelburg Primary School from 1928 to 1930. He then returned to Mozambique and attended a church school for the next two years.