Background It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa. Objective To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies. Methods A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed. Results Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25–1.81) and a family history of stroke (OR 1.20, 1.03–1.39) while Islamic religion (OR=0.82, CI: 0.72–0.94), being currently unmarried (OR = 0.81, CI: 0.70–0.92), and alcohol use (OR = 0.78, CI: 0.67–0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03–1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65–0.96). Conclusion To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.