The ability to produce novel ideas is central to societal progress and innovation; however, little is known about the biological basis of creativity. Here, we investigate the organization of brain networks that support creativity by combining functional neuroimaging data with gene expression information. Given the multifaceted nature of creative thinking, we hypothesized that distributed connectivity would not only be related to individual differences in creative ability, but also delineate the cortical distributions of genes involved in synaptic plasticity. We defined neuroimaging phenotypes using a graph theory approach that detects local and distributed network circuits, then characterized the spatial associations between functional connectivity and cortical gene expression distributions. Our findings reveal strong spatial correlations between connectivity maps and sets of genes devoted to synaptic assembly and signaling. This connectomic-transcriptome approach thus identifies gene expression profiles associated with high creative ability, linking cognitive flexibility to neural plasticity in the human brain.