In this study, a novel operating strategy was developed to improve the separation performance of simulated moving bed (SMB) chromatography by the simultaneous control of product outlet streams and feed inlet stream (SimCon). The SimCon operation can achieve a high separation performance without exceeding the maximum allowable pressure drop in an SMB system. The SimCon operation consisted of three steps within a single switching period: the initial, middle, and last steps. The extract port and feed-inlet port were closed at the initial step, but the raffinate port was closed at the last step. Therefore, in the SimCon strategy, we introduce two additional operating variables in a switching period, namely the middle time and middle length. In the SimCon operation, the middle step is a key factor to achieving a good separation performance because concentration profiles can be well controlled by two new middle-step variables. The SimCon operation showed outstanding results compared with those of the corresponding conventional SMB and other stream-control strategies in terms of purity, recovery, productivity, and eluent consumption. Because the SimCon operation can be operated with smaller flow and pressure fluctuations than other flow-rate-control strategies and improves the column efficiency, it is expected that the strategy can be practically adapted to real SMB processes with a good separation performance.