Substantial research demonstrates the importance of mate choice to speciation, yet we know little about the molecular mechanisms that underpin this crucial decision-making process. Prior research revealed that limnetic and benthic female stickleback fish use different male traits to evaluate prospective partners and they reject heterospecific males based on variation in these displays. We coupled behavioral data from a mate choice experiment with gene expression data from female brains. We find substantial gene expression variation across species, regardless of behavioral context or shared ecology, suggesting general divergence in gene expression patterns in female brains. Intriguingly, female gene co-expression module variation reflects variation in male displays and this occurs in opposing directions for the two species. Our findings suggest male display variation elicits a genomic response that underpins species differences in female preferences and choice behavior. We add important new insights to our understanding of the molecular processes underlying female decision-making that is crucial for reproductive isolation between diverging species.