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River salinization is a byproduct of water resource development that results from cumulative impacts of flow-regime modifications and crop irrigation. However, historical salinization in the Lower Pecos River is often attributed to natural, high-salinity groundwater. Here, evidence from literature and U.S. Geological Survey gaging stations is reviewed to summarize historical changes associated with water development that potentially contributed to Pecos River salinization. A suite of hydrological changes, initiated in the 1880s, likely contributed to streamflow salinization: (1) reduced flood frequency and magnitude, (2) diminished streamflow, (3) increased evapotranspiration, and (4) increased prevalence of natural, high-salinity groundwater. Salinization is presently highest where these cumulative impacts were greatest (Red Bluff Dam to Girvin, Texas). Prior to water-resource development, higher, fresher streamflows and periodic floods diluted natural, high-salinity groundwater inflows and continuously exported salts from the drainage. Predevelopment salinity was low enough to support at least 44 native fishes, 13 of which have disappeared from the region. Only seven euryhaline natives remain in the most salinized river reach. However, flow-regime restoration and improved irrigation practice could potentially reduce salinization and partially restore a freshwater fauna.