Economic downturns, social change, and migrations shape population expansion and shrinkage, making city life cycles particularly complex over time and intrinsically diversified over space. Identifying local drivers of population change plays a major role when addressing metropolitan cycles of growth and decline and provides insights to any policy and planning strategy aimed at promoting together local development, economic competitiveness, and socio-environmental sustainability at large. Timing of metropolitan cycles is, however, heterogeneous and reflects the individual development path of any city. Assuming economic downturns and the associated social processes at the base of spatially heterogeneous patterns of population growth and decline in Mediterranean Europe, we adopted a spatial econometric approach investigating short-term and long-term demographic dynamics (1960–2010) in metropolitan Athens (Greece), with the aim at identifying contextual drivers of population change. Spatial regressions evaluated the role of economic and non-economic dimensions of metropolitan growth, quantifying the impact of agglomeration, scale, accessibility, and amenities at different phases of the city life cycle. Settlement models grounded on scale and agglomeration processes—with growing population in high- and medium-density municipalities—were observed under economic expansion. Recession consolidated a settlement model with population growth in socially dynamic and accessible (low density) districts with natural/cultural amenities, reflecting the inherent decline of agglomeration economies. Based on such dynamics, the polarized hierarchy of central and peripheral locations resulting from radio-centric population expansion was replaced with a settlement model grounded on population increase in “intermediate-density,” attractive locations.