Extensive immunisation plays a critical role in preventing, containing, and stopping transmission of COVID-19, and the success of extensive immunisation hinges on individual acceptance of these approved vaccines. However, in several African countries, people’s reluctance to receive the recommended vaccines remains a major concern. This paper uses a qualitative research approach that included 144 semi-structured interviews to investigate the ways people in Ghana, Malawi, and Cameroon construct and understand risk related to COVID-19 and recommended vaccines. Using the concept of riskscapes, our Findings bring to the fore an alternative geographical understanding of COVID-19 viral spread and COVID-19 vaccines, where spatial, relational, and temporal dimensions of risk are intimately interwoven. Spatiality was important to people’s understanding of risk. People’s understanding of COVID-19 viral spread and COVID-19 vaccine risks was tied to specific sites and landscapes.  The Findings show that vaccine safety goes beyond clinical and regulatory authority approvals; it encompasses forces which are socio-spatial in nature. Additionally, our Findings highlight how power relations are manifested at macro- and micro-structures and operate through different channels to influence COVID-19 vaccine acceptance and rejection. We contend that the multiple manifestations of power relations have implications regarding the individualisation of risk. In some situations, people manifest autonomy regarding managing risk and in other cases that autonomy is challenged through macro and micro power structures. Promoting COVID-19 vaccine uptake requires understanding the socio-spatial perceptions of risk. An in-depth understanding of localised perceptions of COVID-19, including COVID-19 vaccines, leads to contextualised and local public health responses to tackle the current pandemic and future ones.