This paper took the actual bus transportation system as the object, simulated the operating state of the system, replaced all the current diesel engine buses with fuel cell buses using electrolysis-produced hydrogen, and completed the existing timetable and routes. In the study, the numbers of hydrogen production stations and hydrogen storage stations, the maximum hydrogen storage capacity of the buses, the supplementary hydrogen capacity of the buses, and the hydrogen production capacity of the hydrogen storage stations were used as the optimal adjustment parameters for minimizing the ten-year construction and operating costs of the fuel cell bus transportation system by the artificial bee colony algorithm. Two hydrogen supply methods, decentralized and centralized hydrogen production, were analyzed. This paper used the actual bus timetable to simulate the operation of the buses, including 14 transfer stations and 112 routes. The results showed that the use of centralized hydrogen production and partitioned hydrogen production transfer stations could indeed reduce the construction and operating costs of the fuel cell bus transportation system. Compared with the decentralized hydrogen production case, the construction and operating costs could be reduced by 6.9%, 12.3%, and 14.5% with one, two, and three zones for centralized hydrogen production, respectively.