Growth mindset, the belief that one’s abilities can improve through cognitive effort, is an important psychological construct with broad implications for enabling children to reach their highest potential. However, surprisingly little is known about malleability of growth mindset in response to cognitive interventions in children and its neurobiological underpinnings. Here we address critical gaps in our knowledge by investigating behavioral and brain changes in growth mindset associated with a four-week training program designed to enhance foundational, academically relevant, cognitive skills in 7–10-year-old children. Cognitive training significantly enhanced children’s growth mindset. Cross-lagged panel analysis of longitudinal pre- and post-training data revealed that growth mindset prior to training predicted cognitive abilities after training, providing support for the positive role of growth mindset in fostering academic achievement. We then examined training-induced changes in brain response and connectivity associated with problem solving in relation to changes in growth mindset. Children’s gains in growth mindset were associated with increased neural response and functional connectivity of the dorsal anterior cingulate cortex, striatum, and hippocampus, brain regions crucial for cognitive control, motivation, and memory. Plasticity of cortico-striatal circuitry emerged as the strongest predictor of growth mindset gains. Taken together, our study demonstrates that children’s growth mindset can be enhanced by cognitive training, and elucidates the potential neurobiological mechanisms underlying its malleability. Findings provide important insights into effective interventions that simultaneously promote growth mindset and learning during the early stages of cognitive development.