Centralized traffic signal control has long been a challenging, high‐dimensional optimization problem. This study establishes a simulation‐based optimization framework and develops a novel optimization algorithm based on trust region Bayesian optimization (TuRBO), which can efficiently obtain an approximate optimal solution to the high‐dimensional traffic signal control problem. Local Gaussian process (GP), trust region, and Thompson sampling are employed in the TuRBO and contribute considerably to performance in terms of computational speed, solution quality, and scalability. Empirical studies are carried out using data from Mudanjiang and Chengdu, China. The performance of TuRBO is compared with that of Bayesian optimization (BO), genetic algorithm and random sampling. The results show that TuRBO converges the fastest because of its ability to balance exploration and exploitation through the trust region and Thompson sampling. Meanwhile, because TuRBO enables more efficient exploitation through the local GP, the solution quality of TuRBO outperforms others significantly. The average waiting time achieved by TuRBO was 2.84% lower than that achieved by BO. Finally, the method has been successfully extended to a large network with 233‐dimensional spaces and 122 signalized intersections, demonstrating that the developed methodology can deal with high‐dimensional traffic signal control effectively for real case applications.