To what extent are levels of cognitive expertise reflected in differential structural connectivity of the brain? We addressed this question by analyzing the white matter brain structure of experts (mathematicians) versus non-experts (non-mathematicians) using probabilistic tractography. Having mathematicians and non-mathematicians as participant groups enabled us to directly compare profiles of structural connectivity arising from individual levels of expertise in mathematics. Tracking from functional seed regions activated during the processing of complex arithmetic formulas revealed an involvement of various fiber bundles such the inferior fronto-occipital fascicle, arcuate fasciculus/superior longitudinal fasciculus (AF/SLF), cross-hemispheric connections of frontal lobe areas through the corpus callosum and cortico-subcortical connectivity via the bilateral thalamic radiation. With the aim of investigating expertise-dependent structural connectivity, the streamline density was correlated with the level of expertise, defined by automaticity of processing complex mathematics. The results showed that structural integrity of the AF/SLF was higher in individuals with higher automaticity, while stronger cortico-thalamic connectivity was associated with lower levels of automaticity. Therefore, we suggest that expertise in the domain of mathematics is reflected in plastic changes of the brain's white matter structure, possibly reflecting a general principle of cognitive expertise.