The film begins with an elderly Margaret Thatcher, long retired from her position as the first female Prime Minister of the United Kingdom, as she struggles to come to terms with the death of her husband, Denis Thatcher. Battling dementia, she begins to recall the pivotal moments of her life, with Denis often appearing in her hallucinations. Margaret reflects on her early life, her entry into politics, and the defining moments that led her to become a prominent figure on the world stage. Her journey from a grocer's daughter in Grantham to a Member of Parliament is marked by her tenacity and determination to rise in the male-dominated world of British politics.

As the narrative unfolds, the film delves into her leadership during some of the most critical moments in contemporary British history, including the economic turmoil of the 1970s, the Falklands War, and the miners' strike. It portrays her uncompromising leadership style and her controversial policies that led to significant changes in British society. Her struggle against the established norms, sexism in politics, and her own party's resistance are highlighted as she pushes forward her vision of free-market principles. The film depicts her personal sacrifices for her career and the toll that a life of public service takes on her personal life and family relationships, painting a complex picture of a woman who broke ground in a world that was, and often still is, predominantly led by men.