Abstract This study used functional MRI and an artificial language training paradigm to explore sex differences in the processing of a new writing system and how sex determines the optimal neural resource recruitment for visual word learning. Results indicated that males and females achieved equal learning outcome, and their learning curve followed a similar power function. They also showed similar overall activation in the fusiform cortex, a region that has been associated with visual word processing. Despite the absence of sex differences in averaged behavioral performance and neural activation, males and females were found to have different neural predictors of visual word learning. As predicted, left-lateralized fusiform activation predicted visual word learning for males, but not for females, whereas bilateral fusiform activation predicted visual word learning for females, but not males. These results suggest that male and female brains operate differently to achieve the best performance in visual word learning. The individual-differences approach adopted in the present study provides a new and useful perspective to sex differences.