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Background The burden of rheumatic fever (RF) and rheumatic heart disease (RHD) is a significant health concern. Despite being largely preventable, their persistence is strongly linked to gaps in community awareness and preventive practices. This study aimed to assess mothers’ knowledge and attitudes towards RF and RHD and to identify modifiable factors influencing prevention.Methods A cross-sectional study conducted in Najran, Saudi Arabia, among 771 mothers from June to September 2025. Data were collected using a structured self-administered online questionnaire covering basic characteristics, knowledge of RF/RHD and attitudes towards preventive practices. Knowledge levels were categorised to identify major and moderate gaps.Results Overall, 58.8% of mothers demonstrated satisfactory knowledge while 73.3% showed positive attitudes towards preventive practices. However, detailed analysis revealed critical modifiable knowledge gaps, particularly regarding the link between untreated streptococcal infection and RHD (38.0%), susceptibility of children aged 5–15 years (31.9%) and the need for long-term penicillin prophylaxis (28.5%). In contrast, general awareness of preventive practices and common symptoms was relatively adequate. A high proportion of children (86.9%) experienced recurrent sore throat, while only 25.0% of mothers had attended RF/RHD educational programmes, highlighting a mismatch between disease exposure and preventive awareness. Logistic regression analysis identified several significant predictors of knowledge and attitudes (p<0.05). These predictors include maternal age, number of children, educational level, employment status, household income, child’s history of recurrent sore throat and prior participation in RF and RHD educational programmes.Conclusion Despite generally acceptable awareness of preventive practices, substantial gaps persist in critical disease-specific knowledge needed to prevent RF and RHD effectively. These modifiable deficiencies, combined with limited participation in educational programmes, highlight missed opportunities for intervention. Targeted, community-based health education focusing on early treatment of sore throat, high-risk groups and adherence to prophylaxis is essential to reduce the burden of RF and RHD.