The Casas Grandes area in Chihuahua, Mexico and the site of Paquime was the center of one the largest regional systems in the U.S. Southwest and Mexican Northwest (SW/NW) during the Medio period (CE 1200-1450). People participated in local and distant exchange networks with groups in the SW/NW, Mesoamerica, and West Mexico. Our knowledge of which obsidian sources people used in Casas Grandes is limited, despite how obsidian could have derived from many different places. We examine how the use of specific obsidian sources may relate to broader political and economic relationships within the Casas Grandes regional system and its association with the Mimbres and Animas regions of the SW/NW. We sourced 116 artifacts using EDXRF spectrometry from four sites that neighbor Paquime. Results demonstrate people used obsidian from Chihuahua, Sonora, and New Mexico. Furthermore, there were varying levels of social interaction and regional integration because there is diversity in source use at the site level, and Casas Grandes were more connected to the Animas region than Mimbres regarding obsidian resource procurement.