Inorganic arsenic (iAs) and lead (Pb) rank first and second on the U.S. Environmental Protection Agency's priority list of hazardous substances. Both are known neurotoxic metals that cause detrimental effects on brain development and lead to deficits in cognitive function and behavioral performance in children. Studies have indicated a potential link between iAs and Pb exposure and a higher risk for autism spectrum disorder (ASD). To provide further insight into whether developmental exposure to iAs or Pb is associated with ASD, we conducted a systematic review and combined data into a meta-analysis to evaluate the available human evidence on the relationships. We systematically reviewed relevant studies published through December 30, 2018 and identified 14 studies on iAs and 37 studies on Pb exposure and their respective associations with ASD. Among them, 8 (53.3%) and 19 (51.3%) studies reported a positive association for iAs and Pb, respectively, and none reported a sole inverse association. In the following meta-analysis, we found statistically significant higher iAs concentrations, in hair and in blood, for children diagnosed with ASD compared with controls across studies. However, the findings on Pb exposure were inconsistent, with a significant association for hair Pb, no association for urinary Pb, and an inverse association for blood Pb. After considering strengths and limitations of the body of research, we concluded that there is consistent evidence supporting a positive association between early life iAs exposure and diagnosis of ASD and inconsistent evidence for Pb exposure and ASD risk. We believe it is in the best interest of policy makers and the public to reduce exposures to iAs and Pb among pregnant women and children. Further, our research supports the need for large perspective human studies with accurate measurement and determination of the long-term body burden of iAs and Pb exposures to assess the impact of iAs and Pb exposures on ASD risk.