This study comprises the first archaeologically-defined chronological and cultural sequence for central Thailand. Based on collaborative research between the Thai–Italian Lopburi Regional Archaeological Project and the Thai–American Thailand Archaeometallurgy Project, the results of excavations at seven pre- and protohistoric sites that witnessed three millennia of local cultural development, from the early second millennium BC onward, are synthesized herein. This study fills a significant gap in Thailand’s prehistory, also identifying important cultural interactions ranging into southern China and Vietnam that led to the formation during the second millennium BC of a ‘Southeast Asian Interaction Sphere’. This interaction sphere, at the close of the second millennium BC, facilitated the transmission of the knowledge of copper-base metallurgy from southern China into Thailand, where it reached the communities of the Lopburi Region who took advantage of their ore-rich environment. At the end of the first millennium BC, strong South Asian contacts emerge in Southeast Asia. Among this study’s salient contributions is the characterization of these critical prehistoric antecedents, which culminated in a process of localization of exogenous elements, usually termed ‘Indianization’. The impact of this dynamic process was initially felt in central Thailand in the late first millennium BC, leading over time to the rise there, by the mid first millennium AD, of one of Southeast Asia’s first ‘state-like’ entities.