The objective of this study was to evaluate the impact of selected sociodemographic factors on childhood vaccination hesitancy and to define their role according to specific exemptions. This population-based cohort study utilized vaccination rate and sociodemographic data from 1st to 12th grade from 2017 to 2021 for all school districts in Colorado. Data included immunization status and exemptions for each vaccine, race, ethnicity, and free and reduced meal status. Data were evaluated through dimensional analysis and Generalized Linear Mixed Models. School districts with a higher representation of White students had lower immunization rates and use more personal exemptions while school districts with larger Hispanic populations and higher proportions of free and reduced lunches had higher vaccination rates and used more religious exemptions. Black and Pacific Islander populations had higher rates of incomplete vaccination records while Asian American population displayed increased vaccination compliance. Colorado is a robust example of how socioeconomic and cultural differences are important factors with a direct influence on vaccination rates. Future childhood vaccination campaigns and legislation should consider complex socioeconomic and cultural factors.