Although Lyme disease is the most frequently reported vector-borne illness in the United States, recent evidence from the CDC suggests that Lyme disease incidence in the United States may be much higher than reported. Lyme disease symptoms can be mistaken for a wide variety of diseases, which can complicate the diagnosis. To date, no diagnostic criteria analysis has been conducted examining the association between sociodemographic variables (sex and age) and seasonality of infection with the severity and symptomology found in Lyme disease cases. Using the CDC's outbreak investigation model, a primary case/control study was conducted using the ROSS Scale to collect data. Comparisons were made between a Lyme disease-diagnosed group (n = 203) and a convenience sample of non-Lyme disease patients (n = 388). Novel symptom patterns were found to significantly predict a diagnosis of Lyme disease. Odds ratio results revealed a positive association between musculoskeletal (OR = 11; 95% CI), neurological (OR = 12; 95% CI), cognitive (OR = 10; 95% CI), and cutaneous (OR = 144; 95% CI) symptoms frequency and severity and the diagnosis of Lyme disease. In addition, overall symptom frequency and severity scores displayed significant differences between cases and controls, between males and females, and among certain age groups. No correlation was found between symptom frequency and severity with the seasonality of infection. Current diagnostic tools search for antibodies to the Borrelia bacteria, but antibody production takes a few weeks. The results of this study help identify at-risk patients based on the presentation and severity of Lyme disease symptoms when antibodies are not present in measureable quantities in the blood stream, allowing for earlier diagnosis.