By the end of 2021, the COVID-19 pandemic resulted in over 54 million cases and more than 800,000 deaths in the United States, and over 350 million cases and more than 5 million deaths worldwide. The uniqueness and gravity of this pandemic have been reflected in the public health guidelines poorly received by a growing subset of the United States population. These poorly received guidelines, including vaccine receipt, are a highly complex psychosocial issue, and have impacted the successful prevention of disease spread. Given the intricate nature of this important barrier, any single statistical analysis methodologically fails to address all convolutions. Therefore, this study utilized different analytical approaches to understand vaccine motivations and population-level trends. With 12,975 surveys from a state-wide year-long surveillance initiative, we performed three robust statistical analyses to evaluate COVID-19 vaccine hesitancy: principal component analysis, survival analysis and spatial time series analysis. The analytic goal was to utilize complementary mathematical approaches to identify overlapping themes of vaccine hesitancy and vaccine trust in a highly conservative US state. The results indicate that vaccine receipt is influenced by the source of information and the population’s trust in the science and approval process behind the vaccines. This multifaceted statistical approach allowed for methodologically rigorous results that public health professionals and policy makers can directly use to improve vaccine interventions.