The existing relationship between human populations is a function of their migratory and genetic exchange, which will be inversely proportional to the distance separating them. The effect of geographic distance on population structure may be estimated by means of isonymic methods that use information on the surnames present in a territory as an approximation to the distribution of allele frequencies. The objective of this study was to analyze whether the 1801 modification of the political border in an area surrounding the town of Olivenza, which experienced a change of sovereignty from Portugal to Spain, has had a noticeable influence on the migration pattern and isolation by distance in that region. For this purpose, data from marriage records of Olivenza and the neighboring Portuguese municipalities of Alandroal, Juromenha, Elvas, Vila Boim (and Terrugem), Terena, Monsaraz, and Vila Viçosa were analyzed. Rates of diversity and inbreeding coefficients were determined to analyze the population structure before (1775–1801) and after (1802–1825) the change of domain. The results show that after the border modification the migration matrices changed differently according to sex, therefore altering the relationship between the various localities of the territory. In Olivenza inbreeding declined slightly and surnames became more heterogeneous. Moreover, after the change of domain the isolation-by-distance models illustrate a temporal reduction in the relative weight of geographical distance on interpopulation kinship. The political border acted as a factor in population differentiation in the Iberian Peninsula (Spain and Portugal).