Margaret MacMillan was born to Dr Robert Laidlaw MacMillan and Eiluned Carey Evans on 23 December 1943. Her maternal grandfather was Major Sir Thomas J. Carey Evans of the Indian Medical Service. The senior Evans served as personal physician to Rufus Isaacs, 1st Marquess of Reading, during the latter's term as Viceroy of India (1921–26). Her maternal grandmother, Lady Olwen Carey Evans, was a daughter of David Lloyd George, Prime Minister of the United Kingdom, and his first wife, Dame Margaret Lloyd George.

In Canada, MacMillan has served on the boards of Historica,[citation needed] the Canadian Institute for International Affairs, the Atlantic Council of Canada, the Ontario Heritage Foundation, and the Churchill Society for the Advancement of Parliamentary Democracy (Canada).