Located in the north-western extreme of the Iberian northern plateau with the Portugal border on the west, Zamora province is one of the current divisions of the autonomous region of Castile-Leon (Spain). According to natural boundaries and historical records, the province of Zamora can be subdivided into six different regions: Aliste, Benavente, Bajo Duero, Campos-Pan, Sanabria and Sayago. The geography of the area is configured by two major rivers: the Duero that crosses the province in a westeast direction and its affluent the Esla that crosses the province in a northwest-southeast course. In this work, we analyze both surnames of 166,349 individuals from Zamora province. The main goal of this study is to explore the differential weight of historical, demographic, geographic and sociocultural factors in shaping the bio-demographic and genetic structure of this specific population. The highest value of total consanguinity based on random isonymy is observed in Sanabria, which also has the lowest values of heteronymy and the highest intra-population a priori kinship. By contrast, Sayago exhibits the highest value of heteronymy and the lowest intra-population a priori kinship. The consanguinity values observed in Zamora are, in part, related to the population structure. Notwithstanding, the values of non-random consanguinity observed in some municipalities could be associated with particular mating behaviors that favor isonymic marriages. Finally, the results of analyses indicate that the levels of micro-differentiation in the province cannot be considered high; however, some degree of substructure could be deduced. It appears that the current population structure of Zamora has been determined not only by settlement history, geographic distance and geographic boundaries, but also, by land system distribution and population size.