The effect of projected 21st Century climate change on hydrological variables in Old Woman Creek estuary was evaluated using 20 Coupled Model Intercomparison Project Phase 5 (CMIP5) precipitation and temperature projections as input to the Soil and Water Assessment Tool (SWAT). Model calibration and validation was done using the Multi-Objective Evolutionary Algorithm and Pareto Optimization. PRISM climate data for the period 1985 -2014 compared with the average of the 20 CMIP5 models show good agreement in both precipitation and temperature with CMIP5 exhibiting low variability across models. Flow, sediment, and organic nitrogen analyzed from simulations run with PRISM show good correlation with the average of 20 CMIP5 simulations. The performance of each of the 20 CMIP5 inputs to the SWAT model was tested using Euclidean distance relative to their average. The three best CMIP5 models (GFDL-ESM2M, MPI-ESM-MR, EC-EARTH) were used for seasonal analysis. The analysis was done in one past and three future climate windows (1985 -2014, 2018 -2045, 2046 -2075 and 2076 -2100). For the historical period, the result shows an over-estimation of flow, sediment and organic nitrogen from January to March in the SWAT model runs with CMIP5 inputs, relative to runs with the PRISM input. Peak flow, sediment and organic nitrogen were observed changing from winter to spring across the time periods. The expected seasonal and annual changes in each variable over the 21st century have implications for algae growth and general health of the Old Woman Creek estuary.