The link between primary tumor location and overall survival in melanoma has been studied in the past, but its associated population and prognostic significance is less understood. The purpose of this study was to characterize melanoma demographics and disease-specific survival (DSS) in relation to primary tumor site. Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were retrospectively analyzed; from 1973 to 2015, 239,257 patients diagnosed with cutaneous melanoma were included in the study and separated into three cohorts based on primary tumor site. The effect of primary location on melanoma survival was evaluated using Cox proportional hazards models. Tumors were predominantly localized and had a depth of ≤1 mm. Patients diagnosed with tumors originating in the upper and lower extremities had significantly increased DSS probability compared to those of the head and neck. Characteristics, including woman sex, married or widowed status, treated on the Pacific coast, and increasing year of diagnosis, were associated with greater DSS. Conversely, non-white or Hispanic origin, higher age at diagnosis, tumors with increased depth, or nodular or acral melanoma histology were associated with lower DSS. Primary tumor site is a significant predictive factor of DSS in cutaneous melanoma along with additional characteristics supported in our study.