To enhance the power density of proton exchange membrane fuel cells, a high air supply pressure must be maintained at the cathode of the stack. Ultra-high-speed single-stage centrifugal compressors were commonly employed, but this approach was associated with issues of motor overheating and lower efficiency. Two-stage pressurization can reduce the motor speed, but it has the problem of excessive surge flow. Taking a specific two-stage centrifugal compressor for an 80 kW fuel cell as the research object, a collaborative numerical simulation model of the high-pressure stage and low-pressure stage was established. The influence mechanisms of the relative outlet width of the impellers in each stage on the compressor’s flow stability were systematically analyzed, and a collaborative optimization design was conducted. The results indicate that adjusting the relative width of the low-pressure stage impeller outlet has a significant impact on the flow characteristics of the high-pressure stage. The phenomenon of flow instability first occurs in the high-pressure zone. Using a smaller relative width of the impeller outlet in the high-pressure stage compared to the low-pressure stage can effectively improve its flow characteristics and increase the compressor’s surge margin.