The St. Clair-Detroit River waterway connects Lake Huron with Lake Erie in the Great Lakes basin to form part of the international boundary between the United States and Canada. A two-dimensional hydrodynamic model is developed to compute flow velocities and water levels as part of a source water assessment of public water intakes. The model, which uses the generalized finite-element code RMA2, discretizes the waterway into a mesh formed by 13,783 quadratic elements defined by 42,936 nodes. Seven steady-state scenarios are used to calibrate the model by adjusting parameters associated with channel roughness in 25 material zones. An inverse modeling code is used to systematically adjust model parameters and to determine their associated uncertainty by use of nonlinear regression. Calibration results show close agreement between simulated and expected flows in major channels and water levels at gaging stations. Sensitivity analyses describe the amount of information available to estimate individual model parameters, and quantify the utility of flow measurements at selected cross sections and water-level measurements at gaging stations. Further data collection, model calibration analysis, and grid refinements are planned to assess and enhance two-dimensional flow simulation capabilities describing the horizontal flow distributions in St. Clair and Detroit Rivers and circulation patterns in Lake St. Clair.