Genetic algorithms (GAs) are well known optimization methods. However, complicated systems with high dimensional variables, such as long-term reservoir operation, usually prevent the methods from reaching optimal solutions. This study proposes a multi-tier interactive genetic algorithm (MIGA) which decomposes a complicated system (long series) into several small-scale sub-systems (sub-series) with GA applied to each sub-system and the multi-tier (key) information mutually interacts among individual sub-systems to find the optimal solution of long-term reservoir operation. To retain the integrity of the original system, over the multi-tier architecture, an operation strategy is designed to concatenate the primary tier and the allocation tiers by providing key information from the primary tier to the allocation tiers when initializing populations in each sub-system. The Shihmen Reservoir in Taiwan is used as a case study. For comparison, three long-term operation results of a sole GA search and a simulation based on the reservoir rule curves are compared with that of MIGA. The results demonstrate that MIGA is far more efficient than the sole GA and can successfully and efficiently increase the possibility of achieving an optimal solution. The improvement rate of fitness values increases more than 25%, and the computation time dramatically decreases 80% in a 20-year long-term operation case. The MIGA with the flexibility of decomposition strategies proposed in this study can be effectively and suitably used in long-term reservoir operation or systems with similar conditions.