A central focus of modern fisheries management is eradicating invaders that threaten imperiled native fishes. However, vast landscapes and limited funding and personnel resources demand a prioritized approach to management. Brook Stickleback Culaea inconstans (Kirtland, 1840) is an aquatic invasive species in Wyoming, USA, that may pose a risk to native biodiversity. Our aim was to evaluate Brook Stickleback’s invasive potential in the North Platte River drainage. We updated the current distribution of Brook Stickleback, evaluated for possible range expansion, and determined landscape-level habitat drivers and occurrence potential for streams across the North Platte River drainage. Additionally, we examined Brook Stickleback’s spatial overlap with native nongame fishes. At the landscape scale, Brook Stickleback preferred low-gradient streams with moderate disturbance risk. Though we did not find evidence of current Brook Stickleback range expansion 61% of streams in the drainage have landscape-level environmental characteristics that are likely suitable for Brook Stickleback, creating potential for future expansion. Brook Stickleback overlapped spatially with 13 native nongame species, though spatial overlap was less common than expected for species with similar habitat preferences. Our work serves as a case study of the factors to consider when assessing a species’ invasive potential in a previously unstudied region.