Exclusive breastfeeding promotion is one of the most important health initiatives today. The World Health Organization recommends that all babies and young children are breastfed exclusively for their first six months of life and then given nutritious complementary food with continued breastfeeding up to two years of age. The benefits of exclusive breastfeeding have been espoused by several studies. Despite the education and promotion of exclusive breastfeeding by the Ghana Health Service and other agencies some mothers do not exclusively breastfeed their children for the first six months of life. This study, therefore, sought to investigate the factors that are associated with the practice of exclusive breastfeeding among women in the West Mamprusi district of Ghana. A 15x20 community-based cross sectional study was conducted in the district using simple random sampling in selecting 300 breastfeeding mothers with infants 0-6 months of age. Multistage cluster sampling procedure was used in selecting the study communities. Bivariate and multivariate analyses were done to find the determinants of exclusive breastfeeding in the study sample. Results indicated the prevalence of exclusive breastfeeding was 84.3%. Factors that were associated with exclusive breastfeeding were household wealth index (P<0.001, OR=12.3, 95%, CI: 35.43-36.7), antenatal care attendance (P<0.001, OR=10.44, 95%, CI: 32.42-37.21), knowledge of exclusive breastfeeding (P<0.002, OR=7.43, 95%, CI: 0.69-4.54) and place of delivery (P<0.006, OR=12.52, 95%, CI: 12.52-13.56). It emerged thatmajority of the women practised exclusive breastfeeding. Educational level of mothers did not have any influence on the practice of exclusive breastfeeding and was not significantly associated with the practice of exclusive breastfeeding. Antenatal care attendance on the other hand had a significant influence on the practice of exclusive feeding. The study recommends that information and education on exclusive breastfeeding among women not attending ANC and those who do not deliver in a facility be intensified in the entire district.