Optimizing the flood limit water level (FLWL) of reservoirs in sediment-laden rivers under changing water and sediment conditions is an important research topic that could improve comprehensive utilization benefits. Because reservoir operation has multiple objectives in sediment-laden rivers, this study established a water–sediment mathematical model, a comprehensive benefit evaluation model, and an evaluation index system. Taking the Xiaolangdi Reservoir of the Yellow River as an example, the operation mode of the FLWL under changing water and sediment conditions was studied. Under the scenarios of incoming sediment amounts of 300–800 million tons, when using the operation mode of gradually raising the FLWL, the sediment retention period was 4–13 years longer; the lower average annual siltation of the downstream channel and minimum bank-full discharge of the downstream channel after 50 years was larger by 150–260 m3/s than the operation mode of raising the FLWL at one time. However, with enhanced benefits of sediment blocking and siltation reduction, other benefits such as water resources supply, hydropower generation, and ecological improvement are reduced. The average annual number of days that do not meet the downstream water resources supply requirements, irrigation, and ecological improvement was increased by 0.64–2.16 days, and 91–197 million kW·h reduced average annual hydropower generation. The critical amount of incoming sediment was 350 million for conversion between the two FLWL operation modes, and it will increase to 450 million tons if the incoming runoff of the Yellow River increases by 20%. After constructing the Guxian Reservoir in the middle of the Yellow River, the critical amount of incoming sediment will increase to 600 million tons. This study is of great significance for improving the utilization efficiency of water resources and promoting the socio-economic development of river basins.