This paper presents an optimal control strategy for online control of central chilled water systems in complex building air-conditioning systems to enhance their energy efficiency. The optimal control strategy is formulated using a systematic approach by considering the system level and subsystem level characteristics and interactions among the overall system. The requirements and constraints of practical applications are also carefully considered during the development of this strategy. This optimal control strategy consists of the model-based performance predictor (i.e., simplified models), cost estimator (i.e., cost function), optimization technique, supervisory strategy and a number of local control strategies. The local control strategies are used to ensure the robust operation and keep track of control settings considering the dynamic characteristics of the local process environment. The performance of this strategy is tested and evaluated in a simulated virtual environment representing the complex central chilling system in a super high-rise building by comparing it with that of other control strategies. The results showed that this strategy is more energy efficient and cost effective than the other strategies for online applications. This strategy is being implemented in the super high-rise building under study for field application and validation.