The 33 086 ha mixed land use Fall Creek watershed in upstate New York is part of the Great Lakes drainage system. Results from more than 3500 water samples are available in a data set that compiles flow data and measurements of various water quality analytes collected between 1972 and 1995 in all seasons and under all flow regimes in Fall Creek and its tributaries. Data is freely accessible at https://ecommons.cornell.edu/handle/1813/8148 and includes measurements of suspended solids, pH, alkalinity, calcium, magnesium, potassium, sodium, chloride, nitrate nitrogen (NO3‐N), sulphate sulphur (SO4‐S), phosphorus (P) fractions molybdate reactive P (MRP) and total dissolved P (TDP), percent P in sediment, and ammonium nitrogen (NH4‐N). Methods, sub‐watershed areas, and coordinates for sampling sites are also included. The work represented in this data set has made important scientific contributions to understanding of hydrological and biogeochemical processes that influence loading in mixed use watersheds and that have an impact on algal productivity in receiving water bodies. In addition, the work has been foundational for important regulatory and management decisions in the region.