Per- and polyfluoroalkyl substances (PFAS) are persistent, mobile contaminants increasingly detected in freshwater systems, yet their spatial distribution and controlling factors across river networks remain poorly resolved. We assessed PFAS occurrence in surface waters across four Northern Great Plains watersheds: Boxelder Creek (SD), Rapid Creek (SD), the Big Sioux River (SD), and the Missouri River (NE). These systems represent small to large watersheds influenced by varying degrees of urban and agricultural land use. Surface water samples were collected during a synoptic sampling event in June 2025 from upstream, urban, tributary, and downstream reaches and analyzed for 40-43 PFAS using U.S. EPA Method 1633 or EPA Method 537.1, depending on site. PFAS occurrence and summed concentrations varied markedly among watersheds. Boxelder Creek exhibited the highest PFAS signal, although elevated concentrations were confined to a small number of downstream sites, with most locations showing substantially lower levels. The Big Sioux River showed intermediate PFAS occurrence, with substantial spatial heterogeneity and higher concentrations at downstream sites relative to upstream locations. Rapid Creek exhibited fewer detections and lower summed concentrations, while the Missouri River showed minimal PFAS occurrence, with only a single PFAS compound detected per site and consistently low summed concentrations. Across all systems, most targeted PFAS were not detected, indicating that observed PFAS patterns were dominated by a limited subset of compounds rather than broad detection across the analytical suite. We used the EPA National Primary Drinking Water Regulations (NPDWR) benchmarks, including individual Maximum Contaminant Levels for six PFAS and the Hazard Index framework for PFAS mixtures, as health-based reference values to support interpretation of surface water data. While the NPDWR does not apply to surface waters, several urban-influenced sites exhibited concentrations or mixture profiles exceeding drinking-water reference values, highlighting areas where continued monitoring may be warranted. Together, these results demonstrate the value of comparative, watershed-scale monitoring for characterizing PFAS occurrence in river systems. This work provides baseline data to support future investigations of seasonal dynamics, mixture behavior, and potential source differentiation in freshwater environments.