The implementation of COVID-19 vaccination in the United States has revealed substantial disparities driven by geography, socioeconomic status, and political ideology. This study explores how these factors were associated with vaccination intake across 360 counties within four U.S.-Mexico border states with distinct socio-political traits. Using regression analysis and GIS mapping, it evaluates the effects of income, education, employment, age, race, ethnicity, occupation, metro status, border status, and political affiliation on first-dose, full vaccination, and booster rates. First-dose rates were found to be significantly higher in border counties (β = 11.184, p < 0.001) and metropolitan areas (β = 2.246, p = 0.040). Democratic population (β = 0.644, p < 0.001) and per capita income (β = 0.950, p = 0.002) were positively associated with the vaccination. Complete-dose vaccination showed significant results similar to those of the first-dose model. Booster was positively associated with Democratic affiliation (β = 0.206, p < 0.001), high school graduation level (β = 0.172, p = 0.007), and the proportion of individuals aged 65 plus (β = 0.484, p < 0.001). In contrast, it was negatively associated with unemployment rates (β = −0.410, p < 0.001). Race and ethnicity also were related to vaccination outcomes: A higher Black population share was linked to lower first-dose vaccination rates (β = −0.386, p < 0.001), whereas Native American population share was associated with increased vaccination. Booster intake increased with a higher Asian population (β = 0.383, p = 0.001) but slightly declined with a higher White population (β = −0.071, p = 0.019).

Background/Objectives: The implementation of COVID-19 vaccination in the United States has revealed substantial disparities driven by geography, socioeconomic conditions, and political ideology. This study examines the association between these factors and COVID-19 vaccination uptake across 360 counties in four U.S.–Mexico border states, characterized by distinct socio-political traits. Methods: Using county-level data, this study employed multivariable regression analysis and GIS mapping to assess the effects of income, education, employment, age, race, ethnicity, occupation, metropolitan status, border status, and political affiliation on Dose 1, Dose 2, and booster vaccination rates. Results: The analysis showed that Dose 1 vaccination rates were significantly higher in border counties and metropolitan areas. Democratic population share and per capita income were positively associated with vaccination uptake. Dose 2 vaccination rates exhibited patterns similar to those observed for Dose 1. Booster vaccination rates were positively associated with Democratic affiliation, the proportion of the population with at least a high school education, and the share of individuals aged 65 years and older. In contrast, unemployment rates were negatively associated with booster uptake. Racial and ethnic composition was also associated with vaccination outcomes: higher Black population shares were associated with lower Dose 1 vaccination rates, whereas higher Native American population shares were associated with higher vaccination rates. Booster uptake was higher with larger shares of the Asian population but slightly lower with larger shares of the White population. Conclusions: COVID-19 vaccination uptake in U.S.–Mexico border counties was associated with a complex interaction of geographic, socioeconomic, demographic, and political factors. These findings underscore the importance of targeted, context-specific public health strategies to reduce vaccination disparities and improve booster coverage in border regions.