Decision-making takes cognitive effort to evaluate motivation and consequences for actions, while adapting to changing environments. Decision-making strategies begin in a flexible, adaptive state where actions and their consequences are considered. However, as the same behavior is repeated, it becomes routinized and inflexible. The dorsomedial striatum (DMS) and dorsolateral striatum (DLS) of the brain promote flexible and inflexible behaviors, respectively. Chronic stress has been linked to altered circuit activity in the DMS and DLS, and promotes the incidence of inflexible behaviors in humans and rodent models. However, the molecular mechanisms driving inflexible behaviors via the DMS and DLS at baseline and during stress are not well understood. Rodent models of inflexible behavior development consist of reward-motivated volitional actions, known as operant conditioning. In this study, we model flexible and inflexible behaviors in mice using a modified operant conditioning paradigm, where modulating the number of training sessions drives different action strategies. We couple this operant conditioning with exogenous administration of the primary stress hormone, corticosterone (CORT), to model the impact of chronic stress on the development of inflexible behaviors. We demonstrate that chronic CORT administration accelerates the development of inflexible behaviors in male and female mice. Additionally, gene expression analysis in the DMS and DLS reflects altered abundance of plasticity-related genes and brain region-specific epigenetic regulation, providing avenues for future exploration into molecular regulators of behavioral inflexibility. Furthermore, plasticity gene activity reduced in the DMS and increased in genes and brain region-specific epigenetic regulation, providing avenues for future exploration into molecular regulators of behavioral inflexibility. Furthermore, plasticity gene activity reduced in the DMS and increased in the DLS as inflexible behaviors formed in both sexes, corroborating years of circuit and electrophysiological data via gene expression patterns. We also found that gene regulation during operant conditioning or CORT administration differed by sex, suggesting sex-specific striatal sensitivity to these stimuli. These data provide a first glimpse into the molecular regulation of DMS- and DLS-guided action strategy usage, and underscores the need for further investigation into the sex- and brain region-specific gene regulation involved in inflexible behavior development.