Background: Evidence suggests a rise in childhood disability rates across the United States with males and those with lower socioeconomic status bearing greater burden. We investigated childhood disability rates in the Mississippi Delta (MDR) and Appalachian regions (AR) in comparison to other parts of the country. Methods: Using data from the US Census Bureau, we calculated childhood disability rates by type and sex at national, regional, and subregional levels. We used risk ratios (RR) to compare childhood disability rates by sex, type, and region. We generated choropleth maps to represent the geographic distribution of disability. Results: Childhood disability was more prevalent, at the national level, among boys (6.64%) than girls (4.08%). Children in the MDR (boys = 8.60%; girls = 5.08%) and AR (boys = 7.81%; girls = 4.83%) had greater risk of disability than those elsewhere in the country (boys = 6.47%; girls = 3.98%), with rates generally higher in rural compared to urban areas in said regions. Conclusions: Childhood disability affects rural areas of the country more extensively, with the MDR and AR affected to an even greater extent. School-based health centers, in particular, which are disproportionately located in urban areas, could benefit disabled children living in the MDR and AR.