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.

Though according to the Crónica de Sancho IV, Sancho designated María as the sole regent,[2] 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.

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.

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.

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.

At the same time, Diego López V de Haro had possession of the lordship of Vizcaya confirmed, and the infant Juan, who momentarily accepted Fernando IV as sovereign in private, had his properties restored.

Directly after, Prince Juan accompanied Alfonso of the Cerda to Sahagún, where he was proclaimed king of Castile, Toledo, Córdoba, Murcia, and Jaén.

Soon after Alfonso of the Cerda and Prince Juan were crowned, both surrounded the Valladolid municipality of Mayorga, Prince Enrique left at the same time for the Nasrid kingdom of Granada to reach peace between the Granada monarch and Fernando IV, because at the time the Granadans attacked the lands of the king throughout Andalusia, which were defended, among others, by Alonso Pérez de Guzmán.