Background: Vaccine hesitancy has emerged as one of the foremost public health challenges threatening global immunisation goals, particularly in sub-Saharan Africa, where complex socioeconomic, cultural, and informational dynamics impede vaccine uptake.

Objective: This study aims to identify and quantify the sociodemographic, attitudinal, and informational determinants of COVID-19 vaccine hesitancy among adults in sub-Saharan Africa.

Method: A cross-sectional survey design was employed with 420 adult participants selected through stratified random sampling across urban, peri-urban, and rural settings. Data were collected using a validated structured questionnaire and analysed using descriptive statistics and binary logistic regression in SPSS v29.

Key Results: The overall vaccine hesitancy rate was 37.4%. Exposure to misinformation (OR = 3.74, 95% CI: 2.47–5.67), healthcare system distrust (OR = 2.66), and low health literacy (OR = 2.10) were the strongest positive predictors. Tertiary education (OR = 0.44) was a significant protective factor. Hesitancy was substantially higher in rural areas (54.8%) compared with urban areas (30.0%).