An initial inquiry into model-based numeric nitrogen and phosphorus (nutrient) criteria for large rivers is presented. Field data collection and associated modeling were conducted on a segment of the lower Yellowstone River in the northwestern United States to assess the feasibility of deriving numeric nutrient criteria using mechanistic water-quality models. The steady-state one-dimensional model QUAL2K and a transect-based companion model AT2K were calibrated and confirmed against low-flow conditions at a time when river loadings, water column chemistry, and diurnal indicators were approximately steady state. Predictive simulation was then implemented via nutrient perturbation to evaluate the steady-state and diurnal response of the river to incremental nutrient additions. In this first part of a two-part series, we detail our modeling approach, model selection, calibration and confirmation, sensitivity analysis, model outcomes, and associated uncertainty. In the second part (Suplee et al., 2015) we describe the criteria development process using the tools described herein. Both articles provide a fundamental understanding of the process required to develop site-specific numeric nutrient criteria using models in applied regulatory settings.(KEY TERMS: nutrient criteria; model; large river; eutrophication; QUAL2K; AT2K; Monte Carlo; water quality; regulation; Yellowstone River.) Flynn, Kyle F., Michael W. Suplee, Steven C. Chapra, and Hua Tao, 2015. Model-Based Nitrogen and Phosphorus (Nutrient) Criteria for Large Temperate Rivers: 1. Model Development and Application.