Background Pertussis is a toxin-mediated respiratory illness caused by Bordetella pertussis that can result in severe complications and death, particularly in infants. Between 2008 and 2011, children less than 3 months old accounted for 83% of the pertussis deaths in the United States. Understanding the geographic disparities in the distribution of pertussis risk and identifying high risk geographic areas is necessary for guiding resource allocation and public health control strategies. Therefore, this study investigated geographic disparities and temporal changes in pertussis risk in Florida from 2010 to 2018. It also investigated socioeconomic and demographic predictors of the identified disparities. Methods Pertussis data covering the time period 2010-2018 were obtained from Florida HealthCHARTS web interface. Spatial patterns and temporal changes in geographic distribution of pertussis risk were assessed using county-level choropleth maps for the time periods 2010-2012, 2013-2015, 2016-2018 and 2010-2018. Tango's flexible spatial scan statistics were used to identify high-risk spatial clusters which were displayed in maps. Ordinary least squares (OLS) regression was used to identify significant predictors of county-level risk. Residuals of the OLS model were assessed for model assumptions including spatial autocorrelation. Results County-level pertussis risk varied from 0 to 116.31 cases per 100,000 people during the study period. A total of 11 significant (p Conclusion There is evidence that geographic disparities exist and have persisted over time in Florida. This study highlights the application and importance of Geographic Information Systems (GIS) technology and spatial statistical/epidemiological tools in identifying areas of highest disease risk so as to guide resource allocation to reduce health disparities and improve health for all.