Acute exposure to surface nitrogen dioxide (NO2) poses substantial global health risks. Using machine learning, we generated the first global, daily, 1-km-resolution, gap-free surface NO2 data from satellite observations for 2018–2022. Surface NO2 shows strong day-to-day variability, with fluctuations reaching 73% of the global mean. We identify pronounced pollution hotspots and large global inequalities in acute NO2 exposure: although only 28% of inhabited land exceeds the WHO daily guideline (25 μg m-3) at least once per year, these exceedances disproportionately affect more than 61% of the global population and nearly all megacities (98%). When exceedances are aggregated over 7-day and 30-day windows, 77% and 56% of megacities remain exposed. The decline in NO2-affected areas outpaces reductions in population exposure, highlighting the challenge of mitigating impacts in densely populated urban centers. Acute NO2 exposure caused approximately 576,000 (95% CI: 473,000–678,000) premature deaths globally in 2019. COVID-19 strictest lockdowns in 2020 temporarily reduced NO2 levels, but rebounds occurred in 91% of countries by 2022. These results reveal the widespread and under-recognized burden of acute NO2 exposure and emphasize the need for high-resolution global monitoring to support effective pollution control.