The effects of roads on landscapes and wildlife and their ecological processes are substantial and represent a major anthropogenic disruption to the natural environment. Current understanding of the impacts of roads for their strategic management is hampered by a lack of information on 1) the influence of the ecosystems on road effects, 2) the effects of roads on higher-order ecosystem responses (populations and communities), and 3) the overall impacts of roads on ecosystems and their wildlife (on both abiotic and biotic ecosystem components). This study used the Silver City Highway in arid New South Wales, Australia, as a model for a typical road in an arid ecosystem to investigate the ecological effects of arid-zone roads and their management. The study examined the spatial variation of soil, vegetation, kangaroo and small mammal variables in relation to the road, explored the factors contributing to these respective spatial variations, investigated the effects of arid-zone road management on vegetation, assessed the fragmentation effect of the arid-zone road on small mammals, and determined the patterns, causes and effects of kangaroo-vehicle collisions. The study revealed that the arid-zone road influenced most of the variables measured, skewed the population demographics of two kangaroo species, and altered the community composition of small mammals, with two small mammal species listed as threatened in NSW and of national significance (Sminthopsis macroura and Leggadina forresti) negatively impacted by the road. Increases in the amount of water along the road edge drove many of the subsequent effects of the arid-zone road as arid-zone flora and fauna are adapted to exploiting limited and patchily distributed resources. However, current arid-zone road management also influenced vegetation quality, microclimates around the road influenced kangaroo densities and small mammal communities, and kangaroo flight behaviour and temporal variations in traffic volume affected roadkill frequency. Together, these results suggest that roads have a high overall ecological impact in arid ecosystems. Conservation managers need to first rank the impacts of arid-zone roads in order of their conservation importance and need for mitigation, and from there, devise relevant informed management frameworks to target these impacts.