María was the daughter of the infanteAlfonso of Molina and Mayor Alfonso de Meneses. Her paternal grandparents were King Alfonso IX of León and Queen Berengaria of Castile. She married her first cousin-once removed Sancho in 1282, although the matrimonial dispensation for kinship was not previously granted. Upon the death of his father, Alfonso X, the couple became king and queen of Castile and León. She was crowned alongside her husband in the cathedral of Toledo. Although the couple was pressured to separate by Rome and others, Sancho chose to honor his wife and delegated many responsibilities to her, including the regency of their son after his death. His reign was short since he died in 1295.
First regency
After the death of Sancho IV, he was succeeded by their eldest son Ferdinand IV, who was under age. Though according to the Crónica de Sancho IV, Sancho designated María as the sole regent, she was forced to share the regency with Sancho's uncle, Henry the Senator, younger brother of Alfonso X. Ferdinand's rule was challenged by a coalition that included his uncle, John, his cousins the infantes de la Cerda, sons of the infante Ferdinand de la Cerda, eldest son of Alfonso X, as well as King James II of Aragón and King Denis of Portugal. Through marriage alliances, gifts of territories, and shrewd politics María was able to lead Ferdinand's cause to victory, though it did not come easily. María built her own coalition, relying on the Castilian Cortes to confirm her authority and playing the powerful family of Haro against the Laras, who supported the opposition. Civil war continued for several years, and María's coregent Henry was often more of an antagonist than a defender of his great-nephew's cause. Around 1300 the alliance against Ferdinand began to crumble when one of his principal enemies, Juan Núñez de Lara, was captured and later reconciled to the young king. Portugal returned to allegiance with Ferdinand with the promise of a marriage between the Portuguese princess Constance and the young king of Castile. María's victory for her son seemed sealed in 1301, when she finally received a papal bull from Pope Boniface VIII, legitimizing her marriage and her children. Eventually, only Aragon was left to support the claim of Alfonso de la Cerda and his brother, which was finally set aside in a treaty between Castile and Aragon a few years later. María's son died in 1312 and was succeeded by his son, Alfonso XI. As the new king was a minor, Maria became regent again. She died in Valladolid in 1321.