Subsurface tile drainage (TD) is a dominant agriculture water management practice in the United States (US) to enhance crop production in poorly-drained soils. Assessments of field- or watershed-level (<50 km²) hydrologic impacts of tile drainage are becoming common; however, a major gap exists in our understanding of regional (>105 km²) impacts of tile drainage on hydrology. The National Water Model (NWM) is a distributed 1-km resolution hydrological model designed to provide accurate streamflow forecasts at 2.7 million reaches across the US. The current NWM lacks tile drainage representation which adds considerable uncertainty to streamflow forecasts in tile-drained areas. In this study, we quantify the performance of the NWM with a newly incorporated tile drainage scheme over the heavily tile-drained Midwestern US. Implementing a tile drainage scheme enhanced the uncalibrated model performance by about 20% to 50% of the calibrated NWM (Calib). The calibrated NWM with tile drainage (CalibTD) showed enhanced accuracy with higher event hit rates and lower false alarm rates than Calib. CalibTD showed better performance in high-flow estimations as tile drainage increased streamflow peaks (14%), volume (2.3%), and baseflow (11%). Regional water balance analysis indicated that tile drainage significantly reduced surface runoff (-7% to -29%), groundwater recharge (-43% to -50%), evapotranspiration (-7% to -13%), and soil moisture content (-2% to -3%). However, infiltration and soil water storage potential significantly increased with tile drainage. Overall, our findings highlight the importance of incorporating the tile drainage process into the operational configuration of the NWM.