This paper proposes a simulation-based framework for assessing airborne self-separation procedures in flow corridors with consideration of different performance metrics, including air traffic operations, corridor capacity, safety, and environmental impacts. Firstly, the airborne self-separation concept in flow corridors is introduced, followed by an agent-based flow corridor simulation model. Then, data were collected to initialize a parallel-lane flow corridor model connecting A461 upper air route from Beijing to Guangzhou in China which can also simulate aircraft self-separating in the flow corridor. The total control delay, flow corridor throughput, breakout rate, and the CO2 emissions of traffic flow were considered as the impact measurements, and the TOPSIS and entropy method was used to rank the performances of different self-separation procedures. We found that combining multiple objectives into one, the optimum scheme can be obtained to guide the design of self-separation procedures for flow corridors. The research results can be used by airspace managers to dynamically develop appropriate operational procedures and rules for flow corridors given different operational conditions and constraints. Also, the framework proposed in the research may be used to evaluate the design of airspace structure with consideration of multiple objectives.