Flow separation and transitions of separation patterns are common phenomena of nozzles working with a wide Mach range. The maximum thrust method is applied to design the single-expansion ramp nozzle (SERN) for specific operating conditions. The nozzle is used to numerically simulate the transition processes of separation patterns under the linear change in the external flow Mach number and the actual trajectory take-off condition of a rocket-based combined cycle (RBCC), to investigate the mechanism through which the external flow field influences the separation pattern transition during acceleration. The computational fluid dynamics (CFD) method is briefly introduced, followed by experimental validation. Then, the design procedure of SERN is described in detail. The simulation results indicate that as the external Mach number increases, the flow field in the nozzle undergoes transitions from RSS (ramp) to FSS, and finally exhibits a no-flow separation pattern. The rate at which the external Mach number varies has little effect on the transition principle of the nozzle flow separation patterns, but it has a significant effect on the critical Mach number of the transition points. The external flow field of the nozzle has an airflow accumulation effect during acceleration, which can delay the transition of the flow separation pattern.