Parameter sensitivity analysis is a significant part of quantifying model uncertainty, effectively identifying key parameters, and improving the efficiency of parameter optimization. The Soil and Water Assessment Tool (SWAT) model was applied to the upper Heihe River basin (UHRB) in China to simulate the monthly runoff for 11 years (1990–2000). Four typical sensitivity analyses, namely, the Morris screening, Sobol analysis, Fourier amplitude sensitivity test (FAST), and extended Fourier amplitude sensitivity test (EFAST), were used to determine the critical parameters affecting hydrological processes. The results show that the sensitivity parameters defined by the four methods were significantly different, resulting in a specific difference in the simulation effect of the SWAT model. The reason may be the different sampling process, sensitivity index, and calculation principle of each method. The snow-melt base temperature (SMTMP) and snowfall temperature (SFTMP) related to the snow-melt process, the available water capacity of the soil layer (SOL_AWC), saturated hydraulic conductivity (SOL_K), depth from the soil surface to the bottom of the layer (SOL_Z), moist bulk density (SOL_BD), deep aquifer percolation fraction (RCHRG_DP), and threshold depth of water in the shallow aquifer required for return flow to occur (GWQMN) related to the soil water and groundwater movement, baseflow alpha factor for bank storage (ALPHA_BNK) related to the base flow regression, and average slope steepness (HRU_SLP) are all very sensitive parameters. The 10 key parameters were optimized 100 times with the sequential uncertainty fitting procedure version 2 (SUFI-2). The Nash–Sutcliffe efficiency coefficient (NSE), Kling–Gupta efficiency coefficient (KGE), mean square error (MSE), and percentage bias (PBIAS) were 0.89, 200, 8.60, and 0.90, respectively. The simulation results are better than optimizing the sensitive parameters defined by the single method and all the selected parameters. The differences illustrate the rationality and importance of parameter sensitivity analysis for hydrological models and the synthesis of multiple approaches to define sensitive parameters. These conclusions have reference significance in the parameter optimization of the SWAT model when studying alpine rivers by constructing the SWAT model.