This study is the first to systematically review and quantify the effects of physical activity on brain structure and neurophysiological functioning in children. Electronic data bases were searched for relevant studies. Studies that met the following criteria were included: (1) used an RCT or cross-over design, (2) examined the effects of physical activity on brain structure and/or neurophysiological functioning, (3) included children (5–12 years old) (4) included a control group (RCTs) or control condition (cross-over trials). A total of 26 and 20 studies were included in the systematic review and meta-analysis, respectively, representing and accompanying 973 and 782 unique children. Main analyses were separated for short-term and long-term physical activity and for effects on brain structure and neurophysiological functioning with a distinction between children from healthy and clinical populations. We found evidence for significant beneficial effects of long-term physical activity on neurophysiological functioning (d = 0.39, p < 0.001). In addition, short-term physical activity may induce changes in neurophysiological functioning (d = 0.32, p = 0.044), although this evidence showed limited robustness. No meta-analytic evidence was found for positive effects on brain structure. The results underline the importance of physical activity for brain development in children.