Sediment load and its response to the variations of the hydrological elements are important for the healthy utilization of a river. In this study, the response of sediment load to hydrological change was explored in the upstream part of the Lancang-Mekong River, a major transboundary river originating from the Tibetan Plateau and running through China, over the past 50 years. A sediment rating curve for the Jiuzhou Station was developed based on the available SSC-Q (suspended sediment concentration (SSC) and flow) data and trends in annual precipitation, runoff, peak flow (PF), low flow (LF), maximum water level (MWL), and sediment load were analyzed from 1957 to 2006. The correlation analysis method and Random Forest (RF) were adopted to qualitatively and quantitatively quantify the contribution of each hydrological element to the sediment load change. Results indicated that both the runoff and sediment load showed a significantly upward trend, especially after 1979, at the 95% confidence level. The sediment load had significantly positive correlations with runoff, PF, and MWL at the 99% confidence level, respectively. In particular, the sediment load had the largest significant positive correlation with runoff since 1980. Runoff had the largest variable importance to the sediment load change, followed by PF, MWL, precipitation, and LF. The increasing trend in the sediment load was mainly attributed to the increase of runoff in the upstream part of the Lancang-Mekong River since the mid-1980s.