The large amount of turquoise artifacts recovered from archaeological sites in the American Southwest and Mesoamerica suggests that turquoise was an important commodity in pre-Columbian trade networks. However, the spatial and temporal patterns of turquoise exchange networks and the provenance regions of the turquoise in the southwestern United States and Mesoamerica are poorly understood. Turquoise (CuAl6(PO4)4(OH)8•4(H2O)) is a supergene mineral that forms from meteoric water along fractures that are often associated with copper porphyry deposits. This copper-rich mineral can range in color and chemistry within a single sample or deposit. The ability to identify the turquoise resource areas of turquoise artifacts using the stable isotopes of hydrogen (2H/1H) and copper (65Cu/63Cu) has overcome many of the limitations of trace element analyses of complex minerals such as turquoise. The geography and geology of turquoise deposits dictate the isotopic composition of turquoise. Employing the Secondary Ion Mass Spectrometry (SIMS) technique to measure the hydrogen and copper stable isotope ratios in turquoise samples, a comparative reference database consisting of 876 analyses from 21 turquoise resource areas in the western United States was established. Sixty-two turquoise artifacts recovered from Aztec Ruin, Salmon Ruin, and nine sites in Chaco Canyon were analyzed and their isotopic signatures were compared to the reference database identifying the turquoise resource areas of 35 artifacts. These results were compared to pre-existing models of trade and exchange in the American Southwest and models that explain the complex culture history of the inhabitants of these sites. The results showed that turquoise was obtained from several different turquoise provenance regions across the western United States and there are notable differences in the turquoise procurement patterns between the three major great houses and between Pueblo Bonito and the small sites within Chaco Canyon. The results from this study improved the understanding of turquoise trade and relationships among the occupants of important Ancestral Puebloan sites in northwestern New Mexico. The development of the turquoise comparative reference database established the foundation of future research for reconstruction of ancient turquoise trade networks and investigation of turquoise procurement strategies in the American Southwest and Mesoamerica.