Castrillo de la Guareña is a municipality in Spain, located in the province of Zamora within the autonomous community of Castile and León.
It lies in the northern part of the country, in a region characterised by the flat plains and agricultural landscape typical of the Castilian meseta. Like many municipalities in Zamora province, it is a small, rural settlement.
As a municipality, Castrillo de la Guareña forms part of the local administrative structure of the province of Zamora, which in turn belongs to the wider autonomous community of Castile and León.