An intelligent robust controller, which combines a shuffled frog-leaping algorithm (SFLA) and an H∞ control strategy, is designed for a semi-active control system with magnetorheological (MR) dampers to reduce seismic responses of structures. Generally, the performance of mixed-sensitivity H∞ (MSH) control highly depends on expert experience in selecting the parameters of the weighting functions. In this study, as a recently-developed heuristic approach, a multi-objective SFLA with constraints is adopted to search for the optimal weighting functions. In the proposed semi-active control, firstly, based on the Bouc–Wen model, the forward dynamic characteristics of the MR damper are investigated through a series of tensile and compression experiments. Secondly, the MR damper inverse model is developed with an adaptive-network-based fuzzy inference system (ANFIS) technique. Finally, the SFLA-optimized MSH control approach integrated with the ANFIS inverse model is used to suppress the structural vibration. The simulation results for a three-story building model equipped with an MR damper verify that the proposed semi-active control method outperforms fuzzy control and two passive control methods. Besides, with the proposed strategy, the changes in structural parameters and earthquake excitations can be satisfactorily dealt with.