To delineate new directions of urban development in a context of demographic shrinkage in Southern Europe, the present study illustrates a comparative analysis of the demographic balance in metropolitan Athens, Greece (1956–2021). The analysis delineates short-term and long-term dynamics of the natural population balance, considering the impact of the Great Recession and COVID-19 pandemic, and assuming a contemporary increase in gross mortality rates and a marked fertility reduction associated with birth postponement. To address such objectives, we have compared the natural growth of population (the ratio of the total number of births to deaths) at ten year intervals (1956, 1960, 1970, 1980, 1990, 2000, 2009, 2019, 2020, 2021) in 115 municipalities of metropolitan Athens, controlling for the local context. The empirical results of descriptive statistics, spatial analysis, correlation statistics, non-parametric inference, and exploratory multivariate techniques outline the indirect impact of COVID-19 on population dynamics, being in some ways additive to the already observed effects of the Great Recession, reinforcing demographic shrinkage in specific local contexts. The COVID-19 pandemic and the Great Crisis likely accelerated the typical outcomes (population aging and low fertility) of the second demographic transition in Greece. These dynamics are associated with more volatile (and possibly reduced) immigration flows and with enhanced emigration, fueling urban shrinkage and a progressive economic decline of metropolitan regions, as our evidence suggests for Athens. Additional research should ascertain the aggregate, indirect role of pandemics in population dynamics as a proxy of urban and regional decline in European regions exposed to long-term aging.