Dichlorodiphenyl trichloroethane (DDT) is an organochlorine insecticide that is banned internationally except for use as part of Indoor Residual Spraying (IRS) programs to control malaria. Although animal studies show that DDT and its breakdown product dichlorodiphenyl dichloroethylene (DDE) affect the immune system and may cause allergies, no studies have examined this question in populations where IRS is conducted. The aim of our study was to investigate whether prenatal exposure to DDT and DDE is associated with allergy symptoms and diagnose among South African children living in an area where IRS is conducted. To accomplish this aim, we used data from the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), an ongoing birth cohort study of 752 children born between 2012 and 2013 in the rural Vhembe district of Limpopo, South Africa. We measured maternal peripartum serum concentrations of DDT and DDE, and administered a questionnaire to the caregivers of 658 children aged 3.5 years to collect information on allergy symptoms and diagnoses as well as potential confounders using validated instruments. Using multiple logistic regression models, we found positive associations between DDT and DDE serum concentrations and most of the allergy symptoms and diagnoses. Maternal DDT (Odds Ratio [OR] = 1.5 per 10-fold increase, 95% Confidence interval, CI = 1.0, 2.3) and DDE (OR = 1.4, 95% CI = 0.8, 2.4) serum concentrations were most strongly associated with caregiver report of wheezing or whistling in the chest. Concentrations of DDT and/or DDE were also associated with increased odds of children's chests sounding wheezy during or after exercise, itchy rashes coming and going for at least six months, diagnosis of food allergy, and diagnosis of dust or dust mites allergy but confidence intervals crossed the null. Results suggest that prenatal exposure to DDT, and possibly DDE, is associated with elevated odds of wheezing among children from an IRS area.