Continuous use of agricultural chemicals and fertilizers, sporadic sewer overflow events, and an increase in urbanization have led to significant nutrient/pollutant loadings into the semi-arid Arroyo Colorado River basin, which is located in South Texas, U.S. Priority nutrients that require reduction include phosphorus and nitrogen and to mitigate issues of low dissolved oxygen, in some of its river segments. Consequently, the river's potential to support aquatic life has been significantly reduced, thus highlighting the need for restoration. To achieve this restoration, a watershed protection plan was developed, comprising several preventive mitigation measures, including installing green infrastructure (GI) practices. However, for effective reduction of excessive nutrient loadings, there is a need to study the effects of different combinations of GI practices under current and future land use scenarios to guide decisions in implementing the cost-effective infrastructure while considering factors such as the existing drainage system, topography, land use, and streamflow. Therefore, this study coupled the Soil and Water Assessment Tool (SWAT) model with the System for Urban Stormwater Treatment and Analysis Integration (SUSTAIN) model to determine the effects of different combinations of GI practices on the reduction of nitrogen and phosphorus under changing land use conditions in three selected Arroyo Colorado subwatersheds. Two land use maps from the U.S. Geological Survey (USGS) Forecasting Scenarios of land use (FORE-SCE) model for 2050, namely, A1B and B1, were implemented in the coupled SWAT-SUSTAIN model in this study, where the urban area is projected to increase by 6% and 4%, respectively, with respect to the 2018 land use scenario. As expected, runoff, phosphorus, and nitrogen slightly increased with imperviousness. The modeling results showed that implementing either vegetated swales or wet ponds reduces flow and nutrients to meet the Total Maximum Daily Loads (TMDLs) targets, which cost about USD 1.5 million under current land use (2018). Under the 2050 future projected land use changes (A1B scenario), the cost-effective GI practice was implemented in vegetated swales at USD 1.5 million. In contrast, bioretention cells occupied the least land area to achieve the TMDL targets at USD 2 million. Under the B1 scenario of 2050 projected land use, porous pavements were most cost effective at USD 1.5 million to meet the TMDL requirements. This research emphasizes the need for collaboration between stakeholders at the watershed and farm levels to achieve TMDL targets. This study informs decision-makers, city planners, watershed managers, and other stakeholders involved in restoration efforts in the Arroyo Colorado basin.