The Yarlung Zangbo River Basin (YZRB) is a key ecological protection area on the Qinghai-Tibet Plateau (QTP). Determination of the ecosystem service values (ESVs) can help recognize the benefits of sustainable management. It is gradually becoming the main path that constructs plateau spatial planning of integrating ecological protection, and achieves global sustainable development goals (SDGs) in China. In this paper, the spatio-temporal dynamic evolutions of the ESVs were estimated on the multiple scales of “basin, subbasin and watershed” from 1980 to 2015. The main factors influencing ESVs were explored in terms of physical geography, human activities, and climate change. It had been proposed that sustainable spatial planning including ecological protection, basin management, and regional development was urgent to set up. Our results show that the increase in wetland and forest and results in an increase of 9.4% in the ESVs. Attention should be paid to the reduction of water and grassland. Water conservation (WC), waste treatment (WT), and soil formation and conservation (SFC) are the most important ecosystem services in the YZRB. At present, the primary problem is to solve the ESVs decreasing caused by glacier melting, grassland degradation, and desertification in the upper reaches region. The middle reaches should raise the level of supply services. Regulation services should be increased in the lower reaches region on the premise of protecting vegetation. The ESVs in adjacent watersheds are interrelated and the phenomenon of “high agglomeration and low agglomeration” is obvious, existing hot-spots and cold-spots of ESVs. Additionally, when the altitude is 4500–5500 m, the temperature is 3–8°C, and the annual precipitation is 350–650 mm, ESVs could reach its maximum. A framework of sustainable plateau spatial planning could provide references to delimit the ecological protection red line, key ecological function zone, and natural resource asset accounting on the QTP.