We examined factors associated with and reasons for perceived susceptibility to COVID-19 among urban and rural adults in Alabama. We surveyed 575 eligible participants’ engagement in preventive behaviors, concern about COVID-19 in their communities, perceived susceptibility to the virus, and reasons for susceptibility across three response options (Yes, No, and Don’t Know/Not Sure). Bivariate analyses compared characteristics by level of perceived susceptibility to COVID-19. A multinomial logistic regression model evaluated the association of demographics, health insurance coverage, and chronic illness status with perceived susceptibility. Participants’ race, gender, and educational attainment were significantly associated with perceived susceptibility to COVID-19. African Americans and males had higher odds of responding ‘No’, compared to ‘Yes’ and ‘Don’t Know/Not Sure’ than Whites and females. Participants with a high school education and lower had higher odds of responding ‘Don’t Know/Not Sure’ versus ‘Yes’ compared to those with college or higher education. Those unconcerned about COVID-19 in their community had higher odds of responding ‘No’ (OR = 2.51, CI 1.35–4.68) and ‘Don’t Know/Not Sure’ (OR = 2.51, CI 1.26–4.99) versus ‘Yes’, as compared to those who were concerned. Possibility of exposure at work was the most frequent reasons for perceiving themselves susceptible to COVID-19, engagement in recommended preventive measures was the most frequent reason among respondents who indicated ‘No’, and uncertainty/perception that everyone is at risk was the most frequent reason among the ones who indicated ‘Don’t Know/Not Sure’. Results indicate that tailored efforts to heighten perceived susceptibility to COVID-19 among specific demographics are needed.