Mexico has been struck by four pandemics with devastating impacts in terms of infections, mortality and demographic change: the smallpox and measles pandemics, the 1918 influenza pandemic and the coronavirus disease (COVID-19) pandemic. This study explores how these pandemics emerged, spread and affected population health, chiefly through the lenses of mortality and morbidity. A historical demographic perspective is adopted, focusing on Mexico City because of its demographic significance and availability of data. While the role of public health responses is acknowledged, the study emphasizes differential mortality effects, using information from both historical documentation and empirical evidence. Given the scarcity of reliable data for earlier pandemics, the analysis of these events is largely descriptive. A comparative approach highlights recurring patterns in the origin, progression and demographic impact of pandemics across Mexico and its capital. The study also incorporates disaggregated findings within Mexico City, offering insights into internal demographic disparities.