Many social media users express concerns about vaccines and their side effects on Twitter. These concerns lead to a compromise of confidence which brings about vaccine hesitancy. In Africa, vaccine hesitancy is a major challenge faced by health policymakers in the fight against COVID-19. Given that most tweets are geotagged, clustering them according to their sentiments could help identify locations that may likely experience vaccine hesitancy for health policy and planning. In this study, we collected 70 000 geotagged vaccine-related tweets in nine African countries, from December 2020 to February 2022. The tweets were classified into three sentiment classespositive, negative, and neutral. The quality of the classification outputs was achieved using Naíve Bayes (NB), logistic regression (LR), support vector machines (SVMs), decision tree (DT), and K-nearest neighbor (KNN) machine learning classifiers. The LR achieved the highest accuracy of 71% with an average area under the curve of 85%. The point-based location technique was used to calculate the hotspots based on the locations of the classified tweets. Locations with green, red, and gray backgrounds on the map signify a hotspot for positive, negative, and neutral sentiments. The outcome of this research shows that discussions on social media can be analyzed to identify hotspots during a disease outbreak, which could inform health policy in planning and management of vaccine hesitancy in Africa.