Southeast Asian archaeological research often emphasizes upland-lowland dynamics in the development of premodern complex societies. This paper tracks upland-lowland dynamics in Pre-Angkorian (6th-8th century CE) Cambodia by focusing on land-use and economy along the Mekong River. Proto-urban settlements emerged throughout the Tonle Sap and Mekong Delta alluvial plains but also appeared at key centers such as Thala Borivat, Sambor, and Wat Phu along the Mekong River’s more narrow corridors. The diversified economy that involved movement of forest resources and food between these tropical upland-lowland ecotones, observed during the colonial period, emerged by the 6th-7th centuries CE and coincided with political consolidations during the Pre-Angkor period. Analysis of this region suggests that non-Khmer (ethnic minority) swidden agricultural groups who now dominate the uplands have premodern roots in the region. Using upland-lowland settings to study tropical habitation, this archaeological study offers a risk-reduction exchange-based model for understanding Cambodia’s premodern Mekong organization.