Risk analysis protocols for prioritizing the management of non-native species are numerous, yet few incorporate risk and management in the same analysis or accommodate a broad diversity of taxa outside of a specific geographic area. We adapted a protocol that accounts for these factors to address non-native animal species in the Southern California/Northern Baja California Coast Ecoregion near the international border in San Diego County, an area with high indigenous biodiversity and high numbers of species of conservation concern. This stepwise, semi-quantitative protocol is applicable to any animal group in any predefined geographic area, relies on consensus-building among taxonomic experts, and has been vetted through previous use and in peer-reviewed literature. Our results show that the final prioritization was driven mainly by management feasibility, with top-ranked species having multitrophic effects that favor other non-native invaders over native residents. Conditions within the assessment area required some modification to the protocol as it was originally designed, namely a shift in emphasis from eradication to control, given that eradication is implausible for most non-native species in the assessment area. We call attention to taxon-specific issues that surfaced during the analysis, identify areas for improvement in this first-ever risk assessment for invasive animal species in the Natural Communities Conservation Plan/Habitat Conservation Plan (NCCP/HCP) reserve system of San Diego County, and provide suggestions for further refinement of the protocol. This study builds on the effort to standardize risk analysis for invasive species globally, given that many of the same invaders present threats to indigenous biodiversity worldwide.