Understanding variations in malaria transmission and exposure is critical to identify populations at risk and enable better targeting of interventions. The indigenous Batwa of southwestern Uganda have a disproportionate burden of malaria infection compared with their non-indigenous neighbors. To better understand the individual- and community-level determinants of malaria exposure, a seroepidemiological study was conducted in 10 local council cells in Kanungu District, Uganda, in April 2014. The Batwa had twice the odds of being seropositive to two Plasmodium falciparum-specific antigens, apical membrane antigen-1 and merozoite surface protein-119, compared with the non-indigenous Bakiga (odds ratio = 2.08, 95% confidence interval = 1.51-2.88). This trend was found irrespective of altitude level and after controlling for cell location. Seroconversion rates in the Batwa were more than twice those observed in the Bakiga. For the Batwa, multiple factors may be associated with higher exposure to malaria and antibody levels relative to their non-indigenous neighbors.