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To understand patterns of HIV transmission among young black MSM and others in Mississippi.Phylogenetic analysis of HIV-1 polymerase (pol) sequences from 799 antiretroviral-naive persons newly diagnosed with HIV infection in Mississippi during 2005–2008, 130 (16%) of whom were black MSM aged 16–25 years.We identified phylogenetic clusters and used surveillance data to evaluate demographic attributes and risk factors of all persons in clusters that included black MSM aged 16–25 years.We identified 82 phylogenetic clusters, 21 (26%) of which included HIV strains from at least one young black MSM. Of the 69 persons in these clusters, 59 were black MSM and seven were black men with unknown transmission category; the remaining three were MSM of white or Hispanic race/ethnicity. Of these 21 clusters, 10 included residents of one geographic region of Mississippi, whereas 11 included residents of multiple regions or outside of the state.Phylogenetic clusters involving HIV-infected young black MSM were homogeneous with respect to demographic and risk characteristics, suggesting insularity of this population with respect to HIV transmission, but were geographically heterogeneous. Reducing HIV transmission among young black MSM in Mississippi may require prevention strategies that are tailored to young black MSM and those in their sexual networks, and prevention interventions should be delivered in a manner to reach young black MSM throughout the state. Phylogenetic analysis can be a tool for local jurisdictions to understand the transmission dynamics in their areas.