Mathematical modeling of water quality in rivers is an important tool for the planning and management of water resources. Nevertheless, the available models frequently show structural and functional limitations. With the objective of reducing these drawbacks, a new model has been developed to simulate water quality in rivers under unsteady conditions; this model runs on the Vensim PLE® software and can also be operated for steady-state conditions. The following eighteen water quality variables can be simulated: DO, BODc, organic nitrogen (No), ammonia nitrogen (Na), nitrite (Ni), nitrate (Nn), organic and inorganic phosphorus (Fo and Fi, respectively), inorganic solids (Si), phytoplankton (F), zooplankton (Z), bottom algae (A), detritus (D), total coliforms (TC), alkalinity (Al.), total inorganic carbon (TIC), pH, and temperature (T). Methane as well as nitrogen and phosphorus compounds that are present in the aerobic and anaerobic layers of the sediment can also be simulated. Several scenarios were generated for computational simulations produced using the new model by using the QUAL2K program, and, when possible, analytical solutions. The results obtained using the new model strongly supported the results from the QUAL family and analytical solutions.