Chronic obstructive pulmonary disease (COPD) is a chronic, inflammatory respiratory disease that obstructs airflow and decreases lung function and is a leading cause death globally. In the United States (US), the prevalence among adults is 6.2%, but increases with age to 12.8% among those 65 years or older. Florida has one of the largest populations of older adults in the US, accounting for 4.5 million adults 65 years or older. This makes Florida an ideal geographic location for investigating COPD as disease prevalence increases with age. Understanding the geographic disparities in COPD and potential associations between its disparities and environmental factors as well as population characteristics is useful in guiding intervention strategies. Thus, the objectives of this study are to investigate county-level geographic disparities of COPD prevalence in Florida and identify county-level socio-demographic predictors of COPD prevalence. This ecological study was performed in Florida using data obtained from the US Census Bureau, Florida Health CHARTS, and County Health Rankings and Roadmaps. County-level COPD prevalence for 2019 was age-standardized using the direct method and 2020 US population as the standard population. High-prevalence spatial clusters of COPD were identified using Tango's flexible spatial scan statistics. Predictors of county-level COPD prevalence were investigated using multivariable ordinary least squares model built using backwards elimination approach. Multicollinearity of regression coefficients was assessed using variance inflation factor. Shapiro-Wilks, Breusch Pagan, and robust Lagrange Multiplier tests were used to assess for normality, homoskedasticity, and spatial autocorrelation of model residuals, respectively. County-level age-adjusted COPD prevalence ranged from 4.7% (Miami-Dade) to 16.9% (Baker and Bradford) with a median prevalence of 9.6%. A total of 6 high-prevalence clusters with prevalence ratios >1.2 were identified. The primary cluster, which was also the largest geographic cluster that included 13 counties, stretched from Nassau County in north-central Florida to Charlotte County in south-central Florida. However, cluster 2 had the highest prevalence ratio (1.68) and included 10 counties in north-central Florida. Together, the primary cluster and cluster 2 covered most of the counties in north-central Florida. Significant predictors of county-level COPD prevalence were county-level percentage of residents with asthma and the percentage of current smokers. There is evidence of spatial clusters of COPD prevalence in Florida. These patterns are explained, in part, by differences in distribution of some health behaviors (smoking) and co-morbidities (asthma). This information is important for guiding intervention efforts to address the condition, reduce health disparities, and improve population health.