Perchlorate (ClO4−) has synthetic and natural sources. Synthetic ClO4− is released to the environment from its use as an oxidant in military and aerospace applications, and from its presence in a variety of common commercial products, such as safety flares, chlorate herbicides, and fireworks. Natural sources of ClO4− in the environment include imported nitrate fertilizers derived from salt deposits in the Atacama Desert of Chile and indigenous natural ClO4− that accumulates in unsaturated soils and groundwaters in other arid and semi-arid environments, largely from atmospheric deposition. The stable isotope ratios of chlorine (37Cl/35Cl) and oxygen (18O/16O, 17O/16O) and the isotopic abundance of radioactive 36Cl in ClO4− can be used to discriminate these different sources. Perchlorate was previously detected at relatively high concentrations (3.8–34.7 μg/L) in groundwater from many wells in the Boardman-Umatilla area near the Columbia River in northeastern Oregon, which is a semi-arid, highly agricultural, heavily irrigated area that includes several past and current military installations. Eight representative groundwater wells were sampled throughout this region and isotopic characteristics of ClO4− collected from each well were measured along with other chemical and isotopic parameters including tritium and other groundwater age indicators. Isotopic data indicate that indigenous natural ClO4− was present in groundwater from all sampled wells and was the predominant source in five of the wells. Synthetic ClO4− was present in the three remaining wells with natural ClO4−, and a minor fraction of Atacama-fertilizer-derived ClO4− was indicated in one of the wells. Data from this study expand the geographic area of the USA in which indigenous natural ClO4− has been detected to include the semi-arid northwest. This study also illustrates the role of irrigation recharge as a mechanism for producing relatively high concentrations of indigenous natural ClO4− in groundwater by flushing accumulated salts from the unsaturated zone.