Evaluating associations between the five-factor personality domains and resting-state functional connectivity networks (e.g. default mode network, DMN) highlights distributed neurobiological systems linked to behaviorally relevant phenotypes. Establishing these associations can highlight a potential underlying role for these neural pathways in related clinical illness and treatment response. Here, we examined associations between within- and between-network resting-state functional connectivity with functional magnetic resonance imaging and the five-factor personality domains: Openness to experience (Openness), Extraversion, Neuroticism, Agreeableness and Conscientiousness. We included data from 470 resting-state scan sessions and personality assessments in 295 healthy participants. Within- and between-network functional connectivity from 32 a priori defined regions was computed across seven resting-state networks. The association between functional connectivity and personality traits was assessed using generalized least squares. Within-network DMN functional connectivity was significantly negatively associated with trait Openness (regression coefficient = -0.0010; [95% confidence interval] = [-0.0017, -0.0003]; PFWER = 0.033), seemingly driven by association with the Fantasy subfacet. Trait Extraversion was significantly negatively associated with functional connectivity between the visual and dorsal attention networks and positively associated with functional connectivity between the frontoparietal and language networks. Our findings provide evidence that resting-state DMN is associated with trait Openness and gives insight into personality neuroscience.