Many low- and middle-income countries face challenges in attaining adequate levels of vaccination coverage, and the factors driving this under-coverage have not been completely elucidated. In this cross-sectional study, we investigated factors associated with vaccination coverage in Mopani District, Limpopo Province, South Africa. Between July and October 2017, we surveyed 317 caregivers (83% of whom were mothers) of seven-month-old infants in Mopani District about barriers faced when attaining vaccines and attitudes towards vaccination, and reviewed the infants’ documented vaccination history. Caregiver and child demographic data were collected shortly after birth. We described the coverage for vaccines that should be received by age seven months, according to South Africa’s Expanded Programme on Immunization schedule, and explored the relationship between coverage and caregiver characteristics, behavioral factors (e.g. attitudes towards vaccination), and structural factors (e.g. vaccination stock-outs at clinics). We found that caregivers reported positive attitudes towards vaccination, based on a seven-question survey of vaccination attitudes. Although coverage was high for most recommended vaccines, it was low for pneumococcal conjugate vaccine (PCV), with just 36% of children having received it by age seven months. This appears to have been due to PCV stock-outs at government clinics. For vaccines other than PCV, children were more likely to be up-to-date on vaccinations if a community health worker (CHW) had visited their home in the past month (adjusted odds ratio (OR) 1.24, confidence interval (CI) (1.10–1.41); p<0.001) and if the caregiver had more years of schooling (adjusted OR 1.03 (CI 1.01–1.05); p=0.012). We conclude that addressing PCV stock-outs at government clinics in Mopani District is necessary to ensure coverage reaches adequate levels. Additionally, supporting CHW programs may be a productive avenue for improving vaccination coverage.