Despite the relatively short existence of COVID-19, the flailing struggle against the pandemic it created is well documented in media reports and scholarly sources. Little effort, however, has been accorded to the effects of the demographics, particularly the locational and age differences, in the effectiveness perception and support for vaccination, focusing on developing countries such as Nigeria— arguably the most populous state in Africa with one of the highest recorded cases of coronavirus infection in the south of the Sahara. This study investigates the nexus between demographic characteristics, location and age, and perception of COVID-19 effectiveness and support for vaccination. Participants comprising youth (233), middle-aged (97) and senior citizens (46) were drawn from urban and rural parts of the Ancient City of Ile-Ife in Osun State of Nigeria. Considering that the population is homogenous, the research instrument was a uniform questionnaire across all demographic groups in both rural and urban locations. One-way ANOVA test was used to analyse the differences in the groups’ perception of the effectiveness of and support for COVID-19 vaccination. Findings revealed that middle-aged citizens displayed a higher perception of effectiveness and support for vaccination against the pathogen. Also, citizens from urban areas reported greater effectiveness perception and support for vaccination. The overall result attests to the prevailing attitudes of age structure and locations of the people about vaccination against COVID-19. Finally, the study discussed the policy and research implications of the findings.