Examination of historical water-quality data (major cations and anions and total dissolved solids [TDS]) for Rock Creek, located in eastern Nebraska’s saline wetlands north of the Platte River, revealed that concentrations of sodium (Na), chloride (Cl), and TDS increased significantly in the downstream reach below the town of Ceresco, exceeding the U.S. Environmental Protection Agency (USEPA) secondary drinking water standards of 250 mg/L for Cl and 500 mg/L for TDS. Research into the probable source(s) of these inorganic constituents revealed that the Dakota Formation of Late Cretaceous age subcrops in the study area and typically yields water with elevated concentrations of Na, Cl, and TDS in southeastern Nebraska. This brackish to saline water upwells to the surficial aquifer and Rock Creek streambed. Additionally, the significant levels of Na and Cl correlate well with the occurrence of unique saline wetlands along Rock Creek downstream from Ceresco. Public-domain geochemical speciation software codes (Visual MINTEQ and NETPATH) were used to characterize and investigate aqueous geochemistry of Rock Creek discharge and to calculate mixing proportions of Dakota Formation water and stream discharge. The NETPATH output suggests that 3.3%–18% of discharge in Rock Creek approximately 10 km (6.2 mi) southeast of Ceresco, Nebraska, originates from the Dakota Formation and probably the underlying Pennsylvanian bedrock. Hopefully, this paper will be the impetus for an up-to-date, comprehensive, and geochemical-rich data investigation of the Dakota Aquifer’s impact on the inorganic water quality of Rock Creek.