Haixi Mongol and Tibetan Autonomous Prefecture (abbreviated as Haixi) is characterized by ecological fragility. Rapid industrial activities have substantial contributions to Haixi's economy, while bringing huge damage to its ecological environment. Located in the northeast of the Tibetan Plateau, Haixi is one of the most important ecological safety barriers of China and contributes significantly to China's national ecological construction. Based on thermodynamics, emergy synthesis is a useful method applied for environmental accounting. In this study, a systematic study on Haixi's eco-economic system was performed by using emergy synthesis to provide a holistic picture of its current performance. Emergy-based indicators were also adopted to evaluate the sustainability of Haixi's eco-economic system. In addition, temporal analysis of the emergy-based indicators was conducted to provide the historical trend of the performance of Haixi's eco-economic system. The results showed that the total emergy use for supporting Haixi's economy in 2016 was 6.69×10²⁴ sej, which was 1.94 times that of the total emergy used to support Haixi's economy in 2010. The results also showed that the emergy in terms of local nonrenewable resources accounted for more than 90% of the total emergy use for supporting Haixi from 2010 to 2016, whereas the proportion of renewable resources and resources from outside were small. In addition, emergy use per person, emergy density, ratio of emergy to money, and environmental loading ratio increased from 8.84×10¹⁸ sej/person, 1.15×10¹³ sej/m², 3.05×10¹⁴ sej/US $, 103.02 in 2010 to 1.65×10¹⁹ sej/person, 2.22×10¹³ sej/m², 9.12×10¹⁴ sej/US $, 213.47 in 2016, respectively. Meanwhile, emergy yield ratio and the emergy-based sustainability index decreased from 2.66×10³ and 25.84 in 2010 to 1.23×10³ and 5.74 in 2016, respectively. The results obtained from this study indicate that although great progress has been made in the Haixi's economy and local people's living, the development of economy largely depends on local nonrenewable resources and present increasing pressure on the local environment. Thus, it is urgent to explore ways to reduce the overexploitation of nonrenewable resources and to promote Haixi's long-term sustainability development. In addition, results obtained from this study indicate that the emergy exchange ratio of Haixi is less than 1. This result shows that Haixi experienced disadvantages during its trade with other regions from 2010 to 2016. To promote rational exchange of emergy flows, it is important to increase the additional value of Haixi's products.