The core Universal Health Coverage (UHC) objectives are to ensure universal access to healthcare services by reducing all forms of inequalities. However, financial constraints are major barriers to accessing healthcare, especially in countries such as Nigeria and South Africa. The findings of this study may aid in informing and communicating health policy to increase financial access to healthcare and its utilization in South Africa and Nigeria. Nigeria-South Africa bilateral relations in terms of politics, economics and trade are demonstrated in the justification of the study setting selection. The objectives were to estimate the prevalence of health insurance coverage, and to explore the socio-demographic factors associated with health insurance in South Africa and Nigeria. This was a cross-sectional study using the 2018 Nigeria Demographic Health Survey and the 2016 South Africa Demographic Health Survey. The 2018 Nigeria Demographic Health Survey data on 55,132 individuals and the 2016 South Africa Demographic Health Survey on 12,142 individuals were used to investigate the prevalence of health insurance associated with socio-demographic factors. Percentages, frequencies, Chi-square and multivariate logistic regression were e mployed, with a significance level of < 0.05. About 2.8% of the Nigerian population and 13.3% of the South African population were insured (Nigeria: males-3.4%, females-2.7% vs. South Africa: males-13.9%, females-12.8%). The multivariate logistic regression analyses showed that higher education was significantly more likely to be associated with health insurance, independent of other socio-demographic factors in Nigeria (Model I: OR: 1.43; 95% CI: 0.34-1.54, < 0.05; Model II: OR: 1.34; 95% CI: 0.28-1.42, < 0.05) and in South Africa (Model I: OR: 1.33; 95% CI: 0.16-1.66, < 0.05; Model II: OR: 1.76; 95% CI: 0.34-1.82, < 0.05). Respondents with a higher wealth index and who were employed were independently associated with health insurance uptake in Nigeria and South Africa ( < 0.001). Females were more likely to be insured ( < 0.001) than males in both countries, and education had a significant impact on the likelihood of health insurance uptake in high wealth index households among both male and females in Nigeria and South Africa. Health insurance coverage was low in both countries and independently associated with socio-demographic factors such as education, wealth and employment. There is a need for continuous sensitization, educational health interventions and employment opportunities for citizens of both countries to participate in the uptake of wide health insurance coverage.