The quality of the ballast water exchange scheme affects many aspects of a ship, including intact stability, structural strength, building and operational expenses, etc. This paper focuses on developing an optimization methodology for large-scale sequential ballast water exchange. The method of transversely symmetrical ballast water tanks being exchanged simultaneously is adopted, and the potentials of multiple tanks being exchanged at a time are explored. The mathematical model for the symmetrical ballast water exchange problem is built by minimizing the occurred maximum trims, maximum hull girder bending moments, and shearing forces as objectives, and the related safety assessment criteria as constraints. A multiobjective genetic algorithm with some operators specially designed for the problem is presented to obtain a set of approximate Pareto-optimal solutions for engineers to choose from. Finally, a real case study on the symmetrical ballast water exchange of a 176,000 DWT bulk carrier is conducted to illustrate the effectiveness of the proposed approach.