The COVID-19 pandemic has had a significant economic and social impact on Malawi. Promoting vaccination is a key protection measure against COVID-19. Employing the health beliefs model (HBM), this study explores various factors that influence COVID-19 vaccination acceptance (intentions and behavior) among adult residents of Malawi. A semi-structured questionnaire was used for data collection. A field-based survey was conducted among adult residents in Lilongwe, Malawi. Descriptive statistics, linear regression, the Chi-square test, and Pearson’s correlation statistics were used for data analysis. A total of 758 questionnaires were involved. Respondents aged 18–24 (OR = 5.079, 95% CI 2.303–11.202), 25–34 (OR = 2.723, 95% CI 1.363–5.438), urban residents (OR = 1.915, 95% CI 1.151–3.187), graduates/professionals (OR = 1.193, 95% CI 0.857–1.651), health workers (OR = 4.080, 95% CI 1.387–12.000), perceived susceptibility (OR = 1.787, 95% CI 1.226–2.605), perceived benefit (OR = 2.992, 95% CI 1.851–4.834), and action cues (OR = 2.001, 95% CI 1.285–3.115) were predictors for “acceptance of COVID-19 vaccine”. The health belief model structure can be used as a good predictor of vaccine acceptance, especially “perceived susceptibility,” “perceived benefit,” and “action cues”. Strengthening COVID-19 vaccine education in these areas will be an important future intervention.