About nine million Artisanal and Small-scale Gold Mining (ASGM) workers in Africa and people living near ASGM activities are highly exposed to geogenic and anthropogenic potentially toxic elements (PTEs). Despite the hazards and risks posed by ASGM being well characterized, coordinated multidisciplinary environmental characterization with combined public health studies are limited, with often piecemeal and snapshot studies reported, as highlighted by this review. Furthermore, studies are often not connected with efforts to minimize hazards holistically. Given this, we systematically reviewed the scientific literature on human health hazards associated with ASGM in Africa through Google Scholar, Science Direct, and Pubmed databases. One hundred and seventy-three peer-reviewed papers published between 1996 and June 2023 from 30 African countries were identified. Toxicological environmental hazards were reported in 102 peer-reviewed papers, notably As, Cd, CN, Cr, Hg, Pb, respirable SiO2-laden dust, and radionuclides. Exposure to PTEs in human biomonitoring matrices and associated health impacts were documented in 71 papers. Hg was the most reported hazard. Gaps in research robustness, regulation and policy framework, technology, risk detection, surveillance, and management were found. Despite international and in-country mitigation efforts, ASGM-related hazards in Africa are worsening. This review paper highlights the need for coordinated action and multidisciplinary collaborative research to connect dispersed isolated studies to better characterize the associated disease burden associated with ASGM in Africa and sustainably maximize the wider benefits of ASGM whilst protecting public health and the environment.