First-aid practices after a domestic accident are not always known, especially in Africa. This study aimed to measure mothers’ knowledge of emergency procedures and attitudes in the event of domestic accidents in children. We conducted a cross-sectional study in the Orodara health district, Kénédougou province, Burkina Faso, among mothers of children aged 0–14 years. The dependent variable was the mothers’ knowledge of domestic accident first-aid practices, and the independent variables were the sociodemographic characteristics of the households and the mothers. Determinants were identified using linear regression with a threshold of 5%. A total of 798 mothers were surveyed. The mean knowledge score was 6.9 (standard deviation = 1.5) out of 19. Upon our multivariate analysis, the factors associated with the mothers’ knowledge about first-aid practices were the mothers’ age, the number of children under 14 years old living in the same household, the household size, the score for knowledge of non-recommended attitudes, the mothers’ level of education, and the place of residence. This study showed that awareness campaigns, especially in rural areas, seem important in improving mothers’ knowledge of first-aid practices in domestic accidents and, therefore, reducing the morbidity and mortality associated with domestic accidents.