International research on HIV/AIDS showing Sub-Saharan Africa (SS) as the leading host of infected people portends that the rate of its spatial diffusion would be very high in the region. Contrariwise, such studies in SS rural areas that host over 60% of its poor residents are scanty. Focusing on a local region in Nigeria, a country with the highest HIV/AIDS-related deaths in SS, the study examined the disease’s spatial diffusion with roads and residential density patterns to employ a grass-root approach to curb its spread. Data from secondary sources on HIV/AIDS and relevant socio-physical variables were used to descriptively and statistically achieve the set goal. Results revealed that direct relationships existed among rural communities’ number of buildings, land area, population, residential density zones, and clustering patterns of HIV/AIDS cases. This diffusion was spatially reflected along transportation routes, especially at the region’s core where major and minor roads converged and some communities were fused, breeding slums and high density. While the prevalence rate of the disease peaked in 2010, more of its cases were reported in the medium-density transition zone while there was a general decline in its spread afterward across the region. The unstandardized regression coefficient identified the residential density zone as the lead factor in HIV/AIDS dispersal in the study area. To codon HIV/AIDS diffusion in SS local regions, residences along interwoven transportation routes in high-density areas must be first attended to. However, concern must be raised for those in the medium residential density zone, especially places that border the former.