Isabel Ponce de León (died 1367) was a Spanish noblewoman from the Ponce de León family. She was the daughter of Pedro Ponce de León, lord of Pueblo de Asturias, Cangas and Tineo, and Sancha Gil de Chacim.
She was the lady of Villanueva de los Infantes, Castrelo, and Espinosa, and great-great-granddaughter of King Alfonso IX of León.
She married Pedro Fernández de Castro.
Their children were Juana de Castro, who became queen of Castile, and Fernando Ruiz de Castro.