The severity and pervasiveness of the COVID-19 pandemic have necessitated the emergency use of COVID-19 vaccines. Three vaccines have been approved in the United States (USA). However, there is still some hesitancy in COVID-19 vaccine acceptability among some subgroups, including college students. While research is limited on vaccine acceptability behavior among college students, preliminary data suggests hesitancy as being high. This study aimed to explain the correlates of COVID-19 vaccine acceptance among college students who reported hesitancy toward the COVID-19 vaccine and those who did not using the initiation component of the multi-theory model (MTM) of health behavior change. Using a cross-sectional study design, data were collected from a Southern USA University (n = 282) utilizing a valid and reliable 27-item questionnaire in February and March 2021. Almost half (47.5%) of participants reported hesitancy to receive the COVID-19 vaccine. The three constructs of MTM’s initiation model, behavioral confidence (b = 0.089, p < 0.001), participatory dialogue (b = 0.056, p < 0.001), and changes in the physical environment (b = 0.066, p = 0.001) were significantly associated with COVID-19 vaccine acceptance among those who were not hesitant to take the vaccine and accounted for 54.8% of the variance. Among those who were hesitant to take the COVID-19 vaccine, the MTM construct of behavioral confidence (b = 0.022, p < 0.001) was significant along with Republican Party political affiliation (b = −0.464, p = 0.004), which was negatively associated with vaccine acceptance. The model accounted for 60.6% of the variance in intention to take the COVID-19 vaccine. This study provides evidence for the utility of MTM as a timely intervention to design messages for college students to enhance COVID-19 vaccine acceptability.