Recurrent cholera outbreaks in sub-Saharan Africa (SSA) attracted a lot of research interest, raising questions about the effectiveness of current prevention and control methods. However, research on cholera and other water-borne diseases in Africa is dominated by epidemiological studies, while investigations on the environmental drivers and reservoirs of cholera remain scarce. The current discourse relating cholera to the environment in SSA is often limited to the rudimentary statement that, “cholera is caused by the consumption of contaminated water and food”. Yet, beyond this simplistic view, literature elsewhere shows that cholera outbreaks are controlled by its complex interactions with environmental drivers and reservoirs. This brings to question whether cholera can be eradicated in SSA without understanding these complex interactions. The current review seeks to (1) highlight the nature and dynamics of recent cholera outbreaks in SSA, (2) discuss the importance of environmental reservoirs of Vibrio cholerae, and anthropogenic and hydroclimatic drivers in controlling the dynamics of cholera outbreaks, and (3) highlight key knowledge gaps and future research directions, and the need to harness emerging research tools such as modeling, machine learning, data mining, and genomics techniques to better understand the cholera dynamics. By bringing to fore these often-overlooked issues in cholera research, we seek to stimulate discussion, and promote a shift toward cross-disciplinary research on cholera and other water-borne diseases in SSA and beyond.