INTRODUCTION: Fever and cough in under-five children are common and predominately self-limiting illnesses. Inappropriate prescribing of antibiotics in sub-Saharan Africa is a significant public health concern. However, prescription sources and use among children with fever or cough have not been explored. Therefore, we explored the factors associated with the use of antibiotics obtained from prescription and non-prescription sources for children with illnesses associated with fever and cough. METHODS: A secondary data analysis was conducted based on the Demographic and Health Survey (DHS) data from 37 sub-Saharan African countries. A total weighted sample of 18,866 under-five children who had a fever/cough and took antibiotics were considered for this study. Given the hierarchical nature of DHS data and the use of antibiotics prescribed from the formal healthcare setting (> 10%), a multilevel modified poisson regression model was fitted. Deviance was used for model comparison and the model with the lowest deviance value was chosen as the best-fitted model. Variables with p ≤ 0.2 in the bivariable analysis were considered for the multivariable modified poisson regression model. In the multivariable multilevel modified poisson regression model, the Adjusted Prevalence Odds Ratio (APOR) with a 95% Confidence Interval (CI) and p-value < 0.05 were reported to declare a significant association with taking antibiotics for fever/cough prescribed from formal healthcare setting. RESULTS: In sub-Saharan Africa, the proportion of use of antibiotics from informal healthcare setting for fever and cough among under-five children was 67.19% (95% CI: 66.51%, 67.85%). In the multilevel modified poisson regression analysis; residing in a rural area (APOR = 1.08, 95% CI: 1.04, 1.12), a child aged 36-47 months (APOR = 0.94, 95% CI: 0.90, 0.98), a child aged 48-59 months (APOR = 0.89, 95% CI: 0.84, 0.94), maternal primary education (APOR = 0.96, 95% CI: 0.93, 0.99), maternal secondary education (APOR = 0.95, 95% CI: 0.92, 0.99), belonged the middle household wealth status (APOR = 1.07, 95% CI: 1.02, 1.11), maternal exposure to news/electronic media (APR = 1.06, 95% CI: 1.02, 1.10), being from a household with 2 under-five children (APR = 0.94, 95% CI: 0.91, 0.97), being from a household with 3 under-five children (APR = 0.89, 95% CI: 0.85, 0.93), being from a household with 4 under-five children (APR = 0.90, 95% CI: 0.83, 0.98), and children of caregivers who were not involved in decision-making for their child health issues were significantly associated with taking antibiotics prescribed from formal healthcare setting for fever/cough among under-five children. CONCLUSION: Only two-thirds of the antibiotics used for children under five who had fever and cough were prescribed from formal healthcare setting. Our findings underscore the significance of addressing healthcare disparities, improving access to qualified healthcare providers, promoting maternal education, and empowering mothers in healthcare decision-making to ensure appropriate antibiotic use in this vulnerable population. Further research and interventions targeted at these factors are warranted to optimize antibiotic prescribing practices and promote responsible antibiotic use in the management of fever and cough in under-five children.