On 9 April 1812, Guizot married at the Temple de l'Oratoire and the Church of the Madeleine. Pauline de Meulan, Pauline, a woman of letters born in 1773 into an aristocratic family ruined by the Revolution, whom he had known since 1807. They lived in perfect happiness until Pauline's death from tuberculosis on 1 August 1827.

Guizot remarried on 8 November 1828, in the same place, to Eliza Dillon, Eliza was born in 1804, the eldest daughter of Pauline de Meulan's younger sister, Henriette Dillon. Eliza had lived in the Guizot household since 1823. Like her aunt, she was a great help to her husband in his intellectual and political activities. She died on 11 March 1833 of puerperal fever contracted after the birth of their son Guillaume.