Reliable water sources are central to human and environmental health. In south Texas, USA, the Nueces River Basin (NRB) directly or indirectly plays that important role for many counties. Several NRB stream segments are designated as ecologically significant because they serve crucial hydrologic, ecologic, and biologic functions. The hydrologically significant streams recharge the Edwards Aquifer, an essential water source for the region’s agricultural, industrial, and residential activities. Unfortunately, the semiarid to arid south Texas climate leads to large inter-annual precipitation variability which impacts streamflow, and as a consequence, the aquifer’s recharge. In this study, we used a suite of hydrologic metrics to evaluate the NRB’s hydroclimatic trends and assess their potential impacts on the watershed’s ecologically significant stream segments using precipitation and streamflow data from the National Climatic Data Center (NCDC) and Hydroclimatic Data Network (HCDN) respectively from 1970 to 2014. The results consistently showed statistically significant decreasing streamflow for certain low-flow indicators over various temporal scales, likely due to water rights diversions and minimal land use changes. This research could help decision-makers develop the necessary tools to manage water resources in south Texas, given the NRB’s significance as a source of water for domestic consumption and ecological health.