The frequency and severity of extreme heat events are rising globally, posing increasing threats to human health. However, there is limited evidence on how the burden of heat changed through time and which populations are most vulnerable to these changes. Previous studies have evaluated the changing effects of extreme heat on health in Asia and Europe, but in Latin American countries, the evidence is scarce. We explored this question in Mexico, expanding on existing work by evaluating how heat-related exposure, risk, and burden change through time and which subpopulations are most impacted. We combined population-weighted municipality-level temperature estimates from Daymet and mortality data from the Mexican Secretary of Health to estimate exposure and applied a time-stratified case-crossover design to estimate heat-related mortality risk. We calculated attributable deaths to estimate burden across 5-year time periods from 1998 to 2022 by state and subpopulation. We considered the 95th percentile of the municipality’s maximum temperature distribution as our main exposure and evaluated alternate metrics as sensitivity analyses. We find that extreme heat exposure has increased over time, from a municipality-level average of 88 days from 1998–2002 to 119 days from 2018–2022. While the odds of mortality from extreme heat decreased overall (from OR: 1.08, 95% CI: 1.07–1.08 in 1998–2002 to OR: 1.04, 95% CI: 1.04–1.05 in 2018–2022), the total number of deaths attributable to heat increased from 6,340 in 1998-2002 to 13,889 in 2018-2022. Northern and Southeastern states and sub-populations like outdoor workers, the unemployed, and those with no schooling had particularly high risk. Our findings highlight the importance of assessing not only risk but also the burden of extreme heat to understand temporal trends in heat-health impacts. Identifying regions and populations in Mexico at heightened risk through temporal and spatial dimensions can inform targeted adaptation and protective strategies that will be critical in the context of climate change.