African Americans have been disproportionately vaccinated at lower rates, which warrants the development of theory-based interventions to reduce vaccine hesitancy in this group. The fourth-generation theories, e.g., multi-theory model (MTM) of health behavior change, are vital in developing behavioral interventions. Therefore, the current study aims to determine recent trends in COVID-19 vaccination rates and to test the MTM model in predicting the initiation of COVID-19 vaccines among vaccine-hesitant Blacks. A sample of 428 unvaccinated African Americans were recruited through a web-based survey using a 28-item psychometric valid questionnaire. Chi-square, independent-samples-t-test or Welch’s t test, and Pearson’s correlation tests were utilized for the analyses. Hierarchical regression modelling was performed to determine the increment in variation accounted for through addition of predictors over a set of models. Nearly 48% of unvaccinated Blacks reported being vaccine-hesitant. The vaccine-hesitant group was relatively younger (40.5 years ± 15.8 vs. 46.2 years ± 17.4, p < 0.001), were Republicans (22.1% vs. 10.0%, p < 0.001), lived in the North-East region (26.0% vs. 11.4%, p < 0.001) and had religious affiliations other than Christianity (21.2% vs. 13.6%, p = 0.04). The mean scores of perceived advantages ((9.01 ± 3.10 vs. 7.07 ± 3.60, p < 0.001) and behavioral confidence (8.84 ± 3.76 vs. 5.67 ± 4.09, p < 0.001) were higher among vaccine non-hesitant group as opposed to the hesitant ones. In a final regression model, all MTM constructs) predicted nearly 65% of variance in initiating COVID-19 vaccination behavior among the vaccine-hesitant group (adjusted R2 = 0.649, F = 32.944, p < 0.001). With each unit increment in MTM constructs (e.g., participatory dialogue and behavior confidence), the initiation of COVID-19 vaccination among vaccine-hesitant Blacks increased by 0.106 and 0.166 units, respectively. Based on the findings of this study a m-health educational intervention to promote COVID-19 vaccine uptake behavior among Blacks is proposed.