Background Previous reviews show a favourable relationship between physical activity (PA) and brain health in children and youth. The purpose of this systematic review was to extend the generalizability of previous findings using only studies that employed randomized controlled designs in a wider age range. Methods After registration in PROSPERO, PRISMA guidelines were followed. Studies must have used a randomized controlled design; manipulated PA once (i.e., acute) or more (i.e., chronic) in apparently healthy children (1 month-17.99 years); and examined cognitive function, brain function, or brain structure as outcomes. Articles were reviewed for inclusion and data extraction were performed in duplicate. Results Overall, 84 studies from 83 papers with 12,600 unique participants were included (nrange = 10–1,224, Mrange = 0.77–17 years). Studies were mostly rated as low risk of bias. The majority of studies (n = 52) reported at least one favourable cognitive function outcome associated with a PA intervention. Few studies (n = 6) reported an unfavourable outcome. Examining the multiple cognitive function outcomes within each study, PA had mostly no effect (nacute = 29, nchronic = 47) or a mix of favourable and no effects (nacute = 20, nchronic = 27). For brain function, acute PA was associated with no change (n = 2) whereas chronic PA was associated with a mix of increases, decreases, or no change (n = 3). For brain structure, two overlapping studies found either favourable or no effects of chronic PA. Discussion PA is unlikely to harm brain health in children and youth and may confer some benefits. More research is needed to examine the relationship between PA and brain structure and function.