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The General Population Cohort (GPC) in south-western Uganda has a low HIV-1 incidence rate (&lt, 1%). However, new infections continue to emerge. In this research, 3796 HIV-1 pol sequences (GPC: n = 1418, non-GPC sites: n = 1223, Central Uganda: n = 1010 and Eastern Uganda: n = 145) generated between 2003&ndash, 2015 were analysed using phylogenetic methods with demographic data to understand HIV-1 transmission in this cohort and inform the epidemic response. HIV-1 subtype A1 was the most prevalent strain in the GPC area (GPC and non-GPC sites) (39.8%), central (45.9%) and eastern (52.4%) Uganda. However, in the GPC alone, subtype D was the predominant subtype (39.1%). Of the 524 transmission clusters identified by Cluster Picker, all large clusters (&ge, 5 individuals, n = 8) involved individuals from the GPC. In a multivariate analysis, clustering was strongly associated with being female (adjusted Odds Ratio, aOR = 1.28, 95% CI, 1.06&ndash, 1.54), being &gt, 25 years (aOR = 1.52, 95% CI, 1.16&ndash, 2.0) and being a resident in the GPC (aOR = 6.90, 95% CI, 5.22&ndash, 9.21). Phylogeographic analysis showed significant viral dissemination (Bayes Factor test, BF &gt, 3) from the GPC without significant viral introductions (BF &lt, 3) into the GPC. The findings suggest localized HIV-1 transmission in the GPC. Intensifying geographically focused combination interventions in the GPC would contribute towards controlling HIV-1 infections.