When her husband, the chief comuneroJuan López de Padilla, was captured and killed in the battle of Villalar in 1521, she took command in his name and successfully lead the defence of the city of Toledo against the royalist forces until the arrangement of a peaceful surrender of the city six months later.
Pacheco managed to escape to Portugal, where she lived till her death, in March 1531. She was buried in Oporto Cathedral.
Martínez Gil, Fernando (2005). María Pacheco: la mujer valerosa, historia de doña María Pacheco, comunera de Castilla (1497-1531). Volumen 3 de Biografías Castilla-La Mancha. Almud / Centro de Estudios de Castilla-La Mancha, D.L. (Ciudad Real). ISBN 84-934140-1-8.