Positive associations exist between physical activity, cognition, and academic performance in children and adolescents. Further research is required to examine which factors underpin the relationships between physical activity and academic performance. This systematic review aimed to identify, critically appraise, and synthesize findings of studies examining relationships between motor proficiency and academic performance in mathematics and reading in typically developing school-aged children and adolescents. A systematic search of electronic databases was performed to identify relevant studies. Fifty-five eligible articles were critically appraised and key data was extracted and synthesized. Findings support associations between several components of motor proficiency and academic performance in mathematics and reading. There was evidence that fine motor proficiency was significantly and positively associated with academic performance in mathematics and reading, particularly during the early years of school. Significant positive associations were also evident between academic performance and components of gross motor proficiency, specifically speed and agility, upper-limb coordination, and total gross motor scores. Preliminary evidence from a small number of experimental studies suggests motor skill interventions in primary school settings may have a positive impact on academic performance in mathematics and/or reading. Future research should include more robust study designs to explore more extensively the impact of motor skill interventions on academic performance.