Background: Breastfeeding is essential for a child’s growth and existence. World Health Organization (WHO) recommended six months exclusive breastfeeding (EBF) for infant death reduction. However, poor knowledge and negative attitude towards EBF result in a decline in breastfeeding practice which is common in various underdeveloped nations including Nigeria. Objective: To compare the impact of knowledge of breastfeeding practices and attitude towards EBF on the prevalence of EBF among nursing mothers attending immunization clinics in rural and urban regions in Rivers State. Methods: A comparative cross-sectional research with 252 breastfeeding women who attended immunization clinics at the designated health facilities in Obio-Akpor and Emohua LGAs were recruited by systematic sampling. A semi-structured questionnaire was applied for the data collection on socio-demographic factors, knowledge, attitude and breastfeeding practices. The data obtained were analyzed with SPSS version 3.2.2. Results: The overall knowledge of various breastfeeding practices and overall attitude toward EBF among the urban and rural participants were statistically significant (P-values= 0.003 & 0.044) respectively. The prevalence of EBF among breastfeeding mothers in urban and rural regions were (66.7 & 54.0%) respectively (P-value= 0.039). Conclusion: The knowledge of breastfeeding practices and overall positive attitude towards EBF and EBF practices are higher in urban than the rural regions of Rivers State. Recommendations: Breastfeeding practices should be considered as an important aspect of antenatal and postnatal health education. Advocacy on the importance of breastfeeding should be stepped up, especially in rural communities.