Abstract Background Computer programming, the process of designing, writing, and testing executable computer code, is an essential skill in numerous fields. A description of the neural structures engaged and modified during programming skill acquisition could help improve training programs and provide clues to the neural substrates underlying the acquisition of related skills. Methods Fourteen female university students without prior computer programing experience were examined by functional magnetic resonance imaging (fMRI) during the early and late stages of a 5-month ‘Computer Processing’ course. Brain regions involved in task performance and learning were identified by comparing responses to programming and control tasks during the early and late stages. Results The accuracy of programming task performance was significantly improved during the late stage. Various regions of the frontal, temporal, parietal, and occipital cortex as well as several subcortical structures (caudate nuclei and cerebellum) were activated during programming tasks. Brain activity in the right inferior frontal gyrus was greater during the late stage and significantly correlated with task performance. Learning was also associated with a rightward shift in laterality of the bilateral inferior frontal gyri. Although the left inferior frontal gyrus was also highly active during the programming task, there were no learning-induced changes in activity nor a significant correlation between activity and task performance. Conclusion Computer programming learning among novices induces functional neuroplasticity within the right inferior frontal gyrus but not the left inferior gyrus (Broca’s area).