Roads are a widespread feature of anthropogenic landscapes, and roadsides serve as disturbed habitats suitable for ruderal plant species colonization. While roadside plant species are often exotic to a region, in some ecosystems such as the Florida scrub, roadsides are also home to numerous endemic, often imperiled species, that capitalize on open, disturbed habitat. Importantly, the co-occurrence of endemics and exotics along roadsides could threaten the populations of the endemics, yet it is unclear how frequently the two groups co-occur. Here, we conducted vegetation surveys across seven habitat types in the Florida scrub ecosystem to (1) examine the distribution and co-occurrence of scrub endemic and exotic species along sandy roadsides, and (2) determine the factors that best predict the occurrence of endemic and exotic species. We found that sandy roadsides were more frequently colonized by endemic rather than exotic plant species and that endemic and exotic species rarely co-occurred. Endemic species occurrence was best predicted by adjacent habitat type, while exotic species occurrence was best predicted by proximity to likely propagule sources. Overall, our study showed that scrub endemic and exotic species largely establish in distinct roadside areas. Our work informs our understanding of the role of roadside in species conservation as well as the potential role of biotic resistance against exotic species.