Non-native plant species are increasing globally, yet their distribution patterns and environmental drivers remain poorly understood in biodiversity-rich but understudied regions like Central America. In this region, non-native species increasingly affect biodiversity, ecosystem integrity, and conservation efforts, especially when they become invasive. We analyzed the spatial distribution of 751 naturalized plant species using over 42,000 occurrence records across the seven countries in Central America. We evaluated the influence of environmental variables, human population density, protected areas, and life zones on both occurrence and species richness. Human population density emerged as the strongest predictor of naturalized species occurrence and richness, highlighting the role of human activity in facilitating invasions. Annual precipitation was positively associated with occurrences, while species richness declined with increasing temperature and biodiversity integrity. Tropical rainforests and other humid life zones had more naturalized species than expected by chance. Protected areas had fewer naturalized species overall, but a higher species ratio per observation, indicating both conservation value and vulnerability. Rare species were found outside protected zones, particularly in disturbed and urbanized areas. Our findings highlight the need for early detection, targeted management, and strengthened protection strategies, especially in mid-elevation zones and densely populated areas. By identifying key environmental and anthropogenic drivers, this study provides actionable insights for conservation planning and invasive species management in one of the world’s most biodiverse and socio-environmentally vulnerable regions.