Arithmetic ability is critical for daily life, academic achievement, career development, and future economic success. Individual differences in arithmetic skills among children and adolescents are related to variations in brain structures. Most existing studies have used hypothesis-driven region of interest analysis. To identify distributed brain regions related to arithmetic ability, we used data-driven cross-validated predictive models to analyze cross-sectional behavioral and structural MRI data in children and adolescents. The gray matter volume (GMV) of widespread brain regions reliably predicted arithmetic abilities measured by the Comprehensive Mathematical Abilities Test. Furthermore, we applied neuroimaging-transcriptome association analysis to explore transcriptional signatures associated with structural patterns of arithmetic ability. Structural patterns of arithmetic ability primarily correlated with transcriptional profiles enriched for genes involved in transmembrane transport and synaptic signaling. Our findings enhance our understanding of the neural and genetic mechanisms underlying children's arithmetic ability and offer a practical predictor for arithmetic skills during development.