This report presents the results of a compositional study using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to examine central Mexican obsidian procurement at four sites dating to the Formative and Classic periods. The study demonstrates LA-ICP-MS to be a highly accurate obsidian sourcing technique, with results that are directly comparable to instrumental neutron activation analysis. It documents a shift circa 600 B.C. in which Middle Formative villages in Tlaxcala began to obtain obsidian almost exclusively from sources located in the Mesa Central, when they had previously obtained approximately 50 percent from Mesa Central sources and 50 percent from sources located in the Sierra Madre Oriental. This shift broadly coincided with the development of large regional centers in Tlaxcala-Puebla and suggests a linkage between the local political evolution occurring at this time and increased interactions with the Mesa Central economic sphere, including the Basin of Mexico. Obsidian workshop dump deposits next to Teotihuacan’s Moon Pyramid, dating to a millennium later, demonstrate the continued reliance on predominantly Mesa Central sources but also diversified procurement that drew on several sources. The Teotihuacan deposits exhibit the preferential utilization of particular sources depending on the types of implements being produced.