Europe witnessed massive migration away from rural areas throughout the 20th century. Spain was no exception to the rule, albeit with differences in timing and pace, and the population in Cantabria constitutes a paradigmatic case. Here, the rural exodus began early – before the mid-20th century – in some mountainous districts, but reached a peak in the 1960s and continued throughout the following decades. Since the 1990s, population levels in rural municipalities have fallen at a slower rate, while the population of the region as a whole has increased slightly. Disturbingly, the rural population has continued to decline in the early 21st century, in an overall context of almost zero population growth. The demographic trends analyzed here are not only different in time, but also in space. With the partial exception of regional capitals and their neighbouring communities, municipalities in mountain districts have witnessed such a substantial decline in their populations that they have experienced a genuine process of depopulation. This case does not explain the all-similar cases in rural Europe as a whole, but it can help in interpreting other comparable processes in different regions of southern Europe where depopulation reached its maximum in the second half of the 20th century and still continues today.