Background: Breastfeeding is important in child’s development and survival. Exclusive breastfeeding (EBF) period of 6 months has been recommended by World Health Organisation (WHO) to reduce infant mortality. However, socio-cultural factors result in sub-optimal breastfeeding practices in many developing countries including Nigeria. Objective: To compare the effect of socio-cultural factors on the knowledge of breastfeeding practices, attitude towards EBF and EBF practice among nursing mothers attending the child welfare clinic in rural and urban health facilities in Rivers State. Methods: A comparative cross-sectional study involving 252 nursing mothers who attended child welfare clinic at the selected health facilities in Obio-Akpor and Emohua LGAs and were recruited by systematic sampling. Semi-structured questionnaire was used to collect data on socio-demographic factors, knowledge, attitude and practice of breastfeeding. The results were analyzed using SPSS version 3.2.2 with appropriate tables and figures generated. Results: The overall knowledge of various breastfeeding practices (P-value= 0.003) and overall attitudes towards EBF (P-value= 0.044) among the participants were statistically significant. The prevalence of EBF among nursing mothers in the urban and rural areas were 66.7% and 54.0% respectively (P-value= 0.039). The determinants of EBF were age, occupation, education, delivery setting and breastfeeding preference of couples, friends and culture. Conclusion: The knowledge, attitude and practice of various breastfeeding methods are higher in the urban than the rural regions of Rivers State and EBF practice is influenced by socio-cultural factors. Recommendations: Enlightenment on the importance of breastfeeding should be increased especially in the rural communities. The social well-being of individuals which influences EBF practice should be ensured by the government.