Drawing from insights into the variability of complex biologic systems we propose that the health of human populations reflects the interrelationship between underlying vulnerabilities (determined by population-level social and economic factors; e.g., income distribution) and capacities (determined by population-level salutary resources, e.g., social capital) and how populations, shaped by these vulnerabilities and capacities, respond to intermittent stressors (e.g., economic downturns) and protective events (e.g., introduction of a school). Monitoring this dynamic at the population-level can be accomplished by examining not only rates of illness and mortality, but variability in rates, either between populations or within populations over time. We used mortality data from New York City neighborhoods between 1990 and 2001 to test two related hypotheses consistent with this model of population health: (a) There is greater variability in mortality rates at a point in time between neighborhoods that are characterized by socioeconomic vulnerability; and (b) there is greater variability in mortality rates over time within neighborhoods that are characterized by socioeconomic vulnerability. We found that neighborhoods characterized by social and economic vulnerability displayed substantial variability in particular mortality rates. Mortality rates displaying the greatest variability were from causes that may be sensitive to social conditions (e.g., homicide or HIV/AIDS rates). Variability in population health existed both between neighborhoods with underlying vulnerability at one point in time and within vulnerable neighborhoods over time. The results of this analysis are consistent with a theory of underlying socioeconomic vulnerabilities of human populations and suggest that variability in population health may be an important consideration in population health assessment.