Background: Ambient air pollution has been characterized as a leading cause of mortality worldwide and has been associated with cardiovascular and respiratory diseases. There is increasing evidence that short-term exposure to nitrogen dioxide (NO2), is related to adverse health effects and mortality. Methods: We conducted a systematic review of short-term NO2 and daily mortality, which were indexed in PubMed and Embase up to June 2021. We calculated random-effects estimates by different continents and globally, and tested for heterogeneity and publication bias. Results: We included 87 articles in our quantitative analysis. NO2 and all-cause as well as cause-specific mortality were positively associated in the main analysis. For all-cause mortality, a 10 ppb increase in NO2 was associated with a 1.58% (95%CI 1.28%–1.88%, I 2 = 96.3%, Eggers’ test p < 0.01, N = 57) increase in the risk of death. For cause-specific mortality, a 10 ppb increase in NO2 was associated with a 1.72% (95%CI 1.41%–2.04%, I 2 = 87.4%, Eggers’ test p < 0.01, N = 42) increase in cardiovascular mortality and a 2.05% (95%CI 1.52%–2.59%, I 2 = 78.5%, Eggers’ test p < 0.01, N = 38) increase in respiratory mortality. In the sensitivity analysis, the metaestimates for all-cause mortality, cardiovascular and respiratory mortality were nearly identical. The heterogeneity would decline to varying degrees through regional and study-design stratification. Conclusions: This study provides evidence of an association between short-term exposure to NO2, a proxy for traffic-sourced air pollutants, and all-cause, cardiovascular and respiratory mortality.