2019 Novel coronavirus (COVID-19) vaccination rates in the United States have plateaued in specific populations, including rural areas. To improve COVID-19 vaccination rates and to encourage early vaccine uptake in future pandemics, this study aimed to examine vaccine attributes associated with early adoption. Data are from an anonymous online survey of adults using targeted Facebook pages of rural southern Indiana towns in January and February 2021 (n = 286). The diffusion of innovation theory states that the rate of adoption of a product in a specific population is explained by five perceived attributes: relative advantage, compatibility, observability, complexity and trialability. Binary logistic regression analyses were used to examine the association of Diffusion of Innovation theory attributes of the COVID-19 vaccine on early adoption. Results indicated that trialability [odds ratio (OR) = 3.307; 95% confidence interval (CI) = 1.964–5.571; P < 0.001], relative advantage (OR = 2.890; 95% CI = 1.789–4.667; P < 0.001) and compatibility (OR = 2.606; 95% CI = 1.476–4.601; P < 0.001) showed significant independent associations with early adoption. Furthermore, age and political ideology were significant moderators of complexity and relative advantage, respectfully. Health education strategies for early vaccine uptake should focus on building trust in vaccine safety, increasing short-term benefits of vaccination and promoting relatability to personal values.