With the development of overall design methodologies for hypersonic vehicles and their propulsion systems, nozzles should expand airflow in a short length and provide sufficient thrust. Therefore, the large expansion ratio single expansion ramp nozzle (LSERN) is widely used. The form of the overexpanded flow field in the nozzle is complex, under the conditions of nozzle start-up, low speed and low nozzle pressure ratio (NPR), thereby negatively influencing the entire propulsion system. Thus, the nozzle flow separation pattern and the key factors affecting the flow separation pattern also deserve considerable attention. In this study, the design of SERN is completed using the cubic curve design method, and the model is numerically simulated for specific operating conditions to study the flow separation patterns and the transition processes of different patterns. Furthermore, the key factors affecting the various flow separation patterns in the nozzle are investigated in detail. Results show that the LSERN in different NPRs appeared in two types of restricted shock separation (RSS) pattern and free shock separation (FSS) pattern, as well as their corresponding flow separation pattern transition processes. The initial expansion angle and the nozzle length affect the range of NPRs maintained by the FSS pattern. The initial expansion angle affects the pattern of flow separation, whereas the nozzle length remarkably influences the critical NPR during transition.