This study analyzes regional development in one of the poorest provinces in China, Guizhou Province, between 2000 and 2012 using a multiscale and multi-mechanism framework. In general, regional inequality has been declining since 2000. In addition, economic development in Guizhou Province presented spatial agglomeration and club convergence, which shows how the development pattern of core-periphery has been developed between 2006 and 2012. Multilevel regression analysis revealed that industrialization, marketization and investment level were the primary driving forces of regional economic disparity in Guizhou Province. We can get a deeper understanding of the mechanisms involved in regional inequality in Guizhou Province with the multilevel regression models. The influences of decentralization on regional economic disparity were actually relatively weak, and investment level exhibited more importance on the regional inequality when the variable of time was considered. In addition, both the topography and urban-rural differentiation were the two main reasons for forming a core-periphery structure in Guizhou Province.