Background: Sub-optimal breastfeeding practices in-particular exclusive breastfeeding (EBF) still prevail in many developing countries including Cameroon, despite the documented evidence on the vital role of breastfeeding on the health and development of infants. Aim: To identify maternal socio-demographic factors associated with exclusive breastfeeding practice amongst Cameroonian mothers of reproductive age. Methods: Data from a nationally representative sample of mothers (aged 15-49 years) with infants aged between 0-6 months was obtained from the 2004 Cameroon Demographic and Health Survey. Multiple binary logistic regression was used to identify and examine the maternal factors most likely to predict exclusive breastfeeding practice while controlling for potential confounders. Results: Only 18.1% of the mothers practiced EBF. EBF was highest (35.2%) in the 0-1 month old infants and lowest (2.4%) in 6 months old infants (p<0.001). The North region and the Northwest region had the lowest proportion (0%) and highest proportion (52.9%) of EBF practice, respectively (p<0.001). Ethnicity and religion were retained as important maternal predictors of EBF practice in the multivariate analysis (p<0.001). Decreased likelihood of EBF practice was found among mothers who were Kirdis (OR=0.23, 95%CI: 0.11-0.48), Pahouin-Betis (OR=0.56, 95%CI: 0.33-0.94) and Atheist (OR=0.30, 95%CI: 0.11-0.80). Conclusion: Cultural disparities and religion are the major maternal factors that influence EBF practice in Cameroon. However, further research to understand the influence of these cultural practices and beliefs, and religion on EBF practice is recommended in order to guide policy makers and public health organizations in planning appropriate and adequate interventions to improve EBF practice. Keywords: Breastfeeding, under-five mortality, Cameroon.