Rego was born on 26 January 1935 in Lisbon, Portugal. Her father was an electrical engineer who worked for the Marconi Company and was ardently anti-fascist. Although this gave her a comfortable middle-class home, the family was divided in 1936 when her father was posted to work in the United Kingdom. Rego's parents left her behind in Portugal in the care of her grandmother until 1939. Rego's grandmother was to become a significant figure in her life, as she learned from her grandmother and the family made many of the traditional folktales that would one day make their way into her art work.