Factors influencing vaccine uptake in Black individuals remain insufficiently documented. Understanding the role of COVID‐19 related stress, conspiracy theories, health literacy, racial discrimination experiences, and confidence in health authorities can inform programs to increase vaccination coverage. We sought to analyze these factors and vaccine uptake among Black individuals in Canada. A representative sample of 2002 Black individuals from Ontario, Quebec, Alberta, Nova Scotia, New Brunswick, British Columbia, and Manitoba, aged 14 years or older completed questionnaires assessing vaccine uptake, health literacy, conspiracy theories, racial discrimination experiences, COVID‐19‐related stress, and confidence in health authorities. Mediation analyses were conducted to assess (1) the effect of health literacy on COVID‐19 vaccination uptake through confidence and need, COVID‐19 related traumatic stress, and racial discrimination, and (2) the effect of conspiracy beliefs on COVID‐19 vaccination uptake through the same factors. Overall, 69.57% (95% confidence interval, 67.55%–71.59%) of the participants were vaccinated and 83.48% of them received two or more doses. Those aged 55 years and older were less likely to be vaccinated, as well as those residing in British Columbia and Manitoba. Mediation models showed that the association between health literacy and COVID‐19 vaccine uptake was mediated by confidence in health authorities (B = 0.02, p < 0.001), COVID‐19‐related stress (B = −0.02, p < 0.001), and racial discrimination (B = −0.01, p = 0.032), but both direct and total effects were nonsignificant. Lastly, conspiracy beliefs were found to have a partial mediation effect through the same mediators (B = 0.02, p < 0.001, B = −0.02, p < 0.001, B = −0.01, p = 0.011, respectively). These findings highlight the need for targeted interventions to address vaccine hesitancy and inform approaches to improve access to vaccinations among Black communities.