The epidemiological evidence supporting putative associations between air pollution and health-related outcomes continues to grow at an accelerated pace with a considerable heterogeneity and with varying consistency based on the outcomes assessed, the examined surveillance system, and the geographic region. We aimed to evaluate the strength of this evidence base, to identify robust associations as well as to evaluate effect variation. An overview of reviews (umbrella review) methodology was implemented. PubMed and Scopus were systematically screened (inception-3/2020) for systematic reviews and meta-analyses examining the association between air pollutants, including CO, NOX, NO2, O3, PM10, PM2.5, and SO2 and human health outcomes. The quality of systematic reviews was evaluated using AMSTAR. The strength of evidence was categorized as: strong, highly suggestive, suggestive, or weak. The criteria included statistical significance of the random-effects meta-analytical estimate and of the effect estimate of the largest study in a meta-analysis, heterogeneity between studies, 95% prediction intervals, and bias related to small study effects. Seventy-five systematic reviews of low to moderate methodological quality reported 548 meta-analyses on the associations between outdoor air quality and human health. Of these, 57% (N = 313) were not statistically significant. Strong evidence supported 13 associations (2%) between elevated PM2.5, PM10, NO2, and SO2 concentrations and increased risk of cardiorespiratory or pregnancy/birth-related outcomes. Twenty-three (4%) highly suggestive associations were identified on elevated PM2.5, PM10, O3, NO2, and SO2 concentrations and increased risk of cardiorespiratory, kidney, autoimmune, neurodegenerative, cancer or pregnancy/birth-related outcomes. Sixty-seven (12%), and 132 (24%) meta-analyses were graded as suggestive, and weak, respectively. Despite the abundance of research on the association between outdoor air quality and human health, the meta-analyses of epidemiological studies in the field provide evidence to support robust associations only for cardiorespiratory or pregnancy/birth-related outcomes.