Climate change is a primary factor influencing alterations in watershed hydrology. Associated changes in temperature and precipitation can influence the fate and transport of non-point source pollution within a watershed, which complicates the application of best management practices (BMPs) for pollution mitigation. Understanding the sensitivity of BMP implementation as climate change is critical for proper management of water resources. The objective of this study is to understand the effects of BMPs on sediment and nutrient yields in the Meramec River watershed in eastern Missouri, U.S.A due to changes in climate. The Soil and Water Assessment Tool (SWAT) was used to model the flow, sediment and nutrient yields across the watershed. Multi-site calibration (1996-2012) and validation (1981-1995; 2012-2014) gave varied results, ranging from very good to acceptable, for the monthly flow, sediment load, total nitrogen (TN) and total phosphorus (TP). Various BMPs were implemented into the calibrated model in conjunction with climate data from four Coupled Model Intercomparison Project Phase 5(CMIP5) projections to estimate the effects of climate change on watershed yields. Implemented BMPs include riparian buffers, vegetated filter strips, terrace, grassed waterway, and tillage. BMPs were implemented in subwatersheds with high sediment and nutrient outputs as well as relatively high ecological value. Results indicate that BMPs could achieve reductions in a range from 2 to 76% for sediment loss, 1 to 64% for TN loss, and 5 to 54% for TP loss. Among the individual BMPs assessed, vegetated filter strips were most effective when considering the reduction in sediment and nutrient loads. This study highlights the effectiveness of a range of BMPs in reducing the sediment and nutrient loads and provides quantitative measures for determining the most effective individual BMP and the optimal combination of BMPs based on current and future climate scenarios.