After 30 years of devoting her life to Science, Margaret felt that she had contributed the best of her work. Margarets husband, William Huggins died in 1910. She planned to write the biography of her late husband, but never succeeded. Margaret fell ill and underwent various surgeries and spent some time in hospital. Aware of her illness, she decided to donate her scientific and artistic treasures to Wellesley College in the United States. Margaret greatly admired the achievements of American women in the academic world and supported womens education.
Margaret Huggins died on 24 March 1915, at the age of 66. She was cremated and her ashes laid next to Williams at Golders Green Crematorium. Margaret addressed in her will for a memorial to be erected in St. Pauls Cathedral, London, in honor of her husband. This memorial consists of a pair of medallions which are inscribed "William Huggins, astronomer 1824–1910" and the other "Margaret Lindsay Huggins, 1848–1915, his wife and fellow worker". There was a plaque established in 1997 that marks the house she grew up in on 23 Longford Terrace, Monkstown Dublin.