Four tick-borne diseases (TBDs), anaplasmosis, ehrlichiosis, Lyme disease (LD), and Rocky Mountain spotted fever (RMSF), are endemic in Illinois. The prevalence of human and canine cases of all four TBDs rose over the study period with significant differences in geographic distribution within the state. Among human cases, there were associations between cases of RMSF and LD and total forest cover, seasonal precipitation, average mean temperature, racial-ethnic groups, and gender. Estimated annual prevalence of three canine TBDs exceeded human TBD cases significantly in each region. There was concordance in the number of human and canine cases by county of residence, in annual prevalence trends, and in time of year at which they were diagnosed. To account for multiple environmental risk factors and to facilitate early diagnosis of cases, integrated surveillance systems must be developed and communication between veterinarians, physicians, and public health agencies must be improved.