This study examines factors associated with an increasingly poor perception of the novel coronavirus in Africa using a designed electronic questionnaire to collect perception-based information from participants across Africa from twenty-one African countries (and from all five regions of Africa) between 1 and 25 February 2022. The study received 66.7% of responses from West Africa, 12.7% from Central Africa, 4.6% from Southern Africa, 15% from East Africa, and 1% from North Africa. The majority of the participants are Nigerians (56%), 14.1% are Cameroonians, 8.7% are Ghanaians, 9.3% are Kenyans, 2% are South Africans, 2.1% are DR-Congolese, 1.6% are Tanzanians, 1.2% are Rwandans, 0.4% are Burundians, and others are Botswana’s, Chadians, Comoros, Congolese, Gambians, Malawians, South Sudanese, Sierra Leoneans, Ugandans, Zambians, and Zimbabweans. All responses were coded on a five-point Likert scale. The study adopts descriptive statistics, principal component analysis, and binary logistic regression analysis for the data analysis. The descriptive analysis of the study shows that the level of ignorance or poor “perception” of COVID-19 in Africa is very high (87% of individuals sampled). It leads to skepticism towards complying with preventive measures as advised by the WHO and directed by the national government across Africa. We adopted logistic regression analysis to identify the factors associated with a poor perception of the virus in Africa. The study finds that religion (belief or faith) and media misinformation are the two leading significant causes of ignorance or poor “perception” of COVID-19 in Africa, with log odd of 0.4775 (resulting in 1.6120 odd ratios) and 1.3155 (resulting in 3.7265 odd ratios), respectively. The study concludes that if the poor attitude or perception towards complying with the preventive measures continues, COVID-19 cases in Africa may increase beyond the current spread.