Background <p>Exclusive breastfeeding (EBF) plays a crucial role in reducing infant morbidity and mortality, contributing significantly to optimal infant growth and development. The World Health Organisation (WHO) recommends EBF for the first six months of life to ensure infants receive essential nutrients and immunity, particularly in developing countries.</p> Objective <p>This study aims to examine the determinants of exclusive breastfeeding among infants 0–6 months of working mothers in Ghana.</p> Methods <p>This study employed a cross-sectional analytical design using nationally representative data. After data cleaning and application of sampling weights, the final sample comprised 347 infants aged 0–6 months born to working mothers. An adjusted logistic regression model was used to identify factors associated with exclusive breastfeeding, accounting for stratification and the complex survey design.</p> Results <p>The prevalence of exclusive breastfeeding among infants of working mothers in the study was 86.31%. The majority of mothers were aged 25–34 years, with over half having attained secondary education. Antenatal care attendance, maternal education, maternal age, size of child, sex of child, parity, sex of household head, marital status, ethnicity and religion were found to be significant predictors of EBF. However, media exposure, mode of delivery and maternal breast cancer screening history showed no significant association with EBF practices.</p> Conclusion <p>Exclusive breastfeeding prevalence among working mothers in Ghana was relatively high. Strengthening antenatal care services, promoting maternal education and targeting key socio-demographic groups may further sustain and improve exclusive breastfeeding practices to enhance child health outcomes.</p>