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Born Maureen Daisy Helen Moore in Ireland, she lived with her mother and C.S. Lewis (who had a 33-year cohabitation with Maureen's mother, Janie King Askins Moore) for 22 years, until 1940, when she married Leonard James Blake (died 1989). She and her mother had started living with Lewis in late 1918 or early 1919, when she was a 13-year-old schoolgirl and Lewis was a 19 or 20-year-old university student. Lewis’s brother, Warren Lewis, joined the household in 1930. Janie Moore was married, though separated from her husband Courtenay, and remained in that state until her death in 1951, the same year her husband died.

While being trained for the army Lewis shared a room with another cadet, Edward Courtnay Francis "Paddy" Moore (1898–1918). Maureen Moore, Paddy's sister, said that the two made a mutual pact[24] that if either died during the war, the survivor would take care of both their families. Paddy was killed in action in 1918 and Lewis kept his promise. Paddy had earlier introduced Lewis to his mother, Jane King Moore, and a friendship quickly sprang up between Lewis, who was eighteen when they met, and Jane, who was forty-five. The friendship with Moore was particularly important to Lewis while he was recovering from his wounds in hospital, as his father did not visit him.

Lewis lived with and cared for Moore until she was hospitalised in the late 1940s. He routinely introduced her as his "mother", and referred to her as such in letters. Lewis, whose own mother had died when he was a child and whose father was distant, demanding and eccentric, developed a deeply affectionate friendship with Moore.