Local, national, and international health agencies have advocated multi-pronged public health strategies to limit infections and prevent deaths. The availability of safe and effective vaccines is critical in the control of a pandemic. Several adverse events have been reported globally following reception of different vaccines, with limited or no data from Africa. This cross-sectional epidemiological study investigated adverse events following COVID-19 vaccination in Africans from April–June, 2021 using a structured online questionnaire. Out of 1200 participants recruited, a total of 80.8% (n = 969) respondents from 35 countries, including 22 African countries and 13 countries where Africans live in the diaspora, reported adverse events. Over half of the vaccinees were male (53.0%) and frontline healthcare workers (55.7%), respectively. A total of 15.6% (n = 151) reported previous exposure to SARS-CoV-2, while about one-fourth, 24.8% (n = 240), reported different underlying health conditions prior to vaccination. Fatal cases were 5.1% (n = 49), while other significant heterogenous events were reported in three categories: very common, common, and uncommon, with the latter including enlarged lymph nodes 2.4% (n = 23), menstrual disorder 0.5% (n = 5), and increased libido 0.2% (n = 2). The study provided useful data for concerned authorities and institutions to prepare plans that will address issues related to COVID-19 vaccines.