Background: Online gaming is a complex and competitive activity. However, little attention has been paid to brain activities relating to gaming proficiency. Methods: In the current study, fMRI data were obtained from 70 subjects while they were playing online games. Based on their playing, we selected 24 clips from each subject for three levels of gaming proficiency (good, poor, and average), with each clip lasting for 8 seconds. Results: When comparing the brain responses during the three conditions, good-play trials, relative to poor-or average-play trials, were associated with greater activation of the declive, postcentral gyrus, and striatum. In post-hoc analyses taking the identified clusters as regions of interest to calculate their functional connectivity, activation of the declive during good-play conditions was associated with that in the precentral gyrus and thalamus, and activation in the striatum was associated with that in the inferior frontal gyrus and middle frontal cortex. Conclusions: Taken together, findings suggest specific regional brain activations and functional connectivity patterns involving brain regions and circuits involved in sensory, motor, automatic and executive functioning and their coordination are associated with better gaming. Specifically, for basic functions, such as simple reaction, motor control, and motor coordination, people need to perform them automatically; for highly cognitive functions, such as plan and strategic playing, people need to engage more executive functions in finishing these works. The automatically processed basic functions spare cognitive resources for the highly cognitive functions, which facilitates their gaming behaviors.