The dynamic change in regional water resource carrying capacity (WRCC) is an important factor in formulating an optimal water resource allocation scheme. To accurately predict the dynamic change in WRCC and formulate the optimal regulation scheme in a river basin, this paper proposes a diagnostic index system of WRCC based on the mutual feeding mechanism of economic-society, water resources and eco-environment. The multi-methods including support vector machine (SV) and system dynamics (SD), back propagation neural network (BP), etc., were used to construct a quantitative dynamic prediction model for the WRCC. The orthogonal test (OT) method is used to optimize the WRCC regulation scheme. Through simulation, the WRCC in the sub-regions of the Yellow River Basin in 2030, 2035 and 2050 under different scenarios are obtained. The study results show that the WRCC in the upper, middle and lower reaches of the Yellow River Basin are overloaded or seriously overloaded before the operation of the Western Line of South-to-North Water Transfer Project (WLSNWTP). Six key driving indexes (unconventional water utilization, water flow into the sea, irrigation water use, irrigation area, industrial added value and water consumption of 10 thousand Yuan (CNY) industrial added value) are selected to carry out orthogonal tests, and the optimal WRCC regulation scheme is obtained in different level years. The present study results have an important reference value for efficient water resource utilization and eco-society development in the Yellow River Basin.