BackgroundUnderstanding knowledge and sentiment toward influenza and vaccination is important for effective health messages and prevention strategies. We aimed to characterize knowledge, attitudes, and practices surrounding influenza illness and vaccination in two South African communities and explore reasons for vaccine hesitancy.MethodsHousehold primary caregivers in Soweto and Klerksdorp townships were interviewed about knowledge of influenza and intention to receive an influenza vaccine using a structured questionnaire. Factors associated with unwillingness to receive vaccine were explored using multivariable regression.ResultsWe interviewed representatives of 973 households in Soweto and 1,442 in Klerksdorp. Most respondents in Soweto (692, 71%) and Klerksdorp (1247, 87%) thought weather or cold caused influenza. While most would get a free influenza vaccine, those unwilling to receive vaccine had concerns about efficacy (Soweto: 19%; Klerksdorp: 19%) and safety (Soweto: 17%; Klerksdorp: 10%). In Soweto, females (aRR 2·0, 95% CI 1·3–3·2) and those with higher household income (aRR 1·8, 95% CI 1·2–2·7) were less willing to receive vaccine. In Klerksdorp, more educated respondents (aRR 1·6, 95% CI 1·1–2·4) were less willing to receive vaccine; households reporting an HIV‐positive member were more willing to receive vaccine (aRR 0·3, 95% CI 0·1–0·8).ConclusionsAlthough findings suggest most community participants were amenable to influenza vaccination, knowledge gaps were present. Emphasizing the importance of influenza as a health problem and addressing vaccine safety and efficacy concerns may improve uptake. Populations less amenable to vaccination, including those with higher education and income, may benefit from targeted messaging efforts.