Objectives To disseminate knowledge of social and behavioral factors influencing exclusive breastfeeding to guide national nutrition programs in West and Central Africa. Methods We searched literature up to August 2018 using pre-defined search terms on PubMed, Google Scholar, Popline and The Cochrane Library. We identified 225 references, representing 19 of the 24 countries in West and Central Africa. Most were from Nigeria (n = 108) and Ghana (n = 45). We used thematic content analysis to synthesize quantitative and qualitative findings separately. Results Factors influencing exclusive breastfeeding in first 6 months of life were divided into individual, setting and structural levels using the 2016 Lancet conceptual model. Socio-economic attributes, perceptions, beliefs and mother-infant interactions were important at the individual level. Misconceptions around breastmilk's quality and availability (quantity) were factors that influenced mothers to give infants water or other liquids. At the setting level, women's autonomy and grandmothers influenced infant feeding decisions in many families. At the structural level, work was an obstacle to achieving exclusive breastfeeding for women in both formal and informal sectors. Social norms generally supported breastfeeding; however, exclusive breastfeeding was challenged by multiple beliefs, including that giving water quenches thirst and “water is life”. Conclusions This work provided a comprehensive review of peer-reviewed and grey literature on the “Factors Influencing the Practice of Exclusive Breastfeeding and Giving Water in West and Central Africa”. The review provides insights on facilitators as well as the many reasons preventing exclusive breastfeeding and provided evidence for the Stronger With Breastmilk Only regional initiative. Disseminating this knowledge among government stakeholders and their partners will mobilize action to achieve the exclusive breastfeeding WHA 2025 and SDG 2030 targets in the subregion, where only one-third of infants (0–5 months) receive breastmilk only (UNICEF, 2021). Funding Sources Bill & Melinda Gates Foundation through Alive & Thrive, managed by FHI Solutions, and UNICEF, West and Central Africa RISING Initiative.