The traditional high-Reynolds-number (Re) effects simulation method for wind effects on circular cylindrical models in wind tunnels is fundamentally a trial-and-error practice, which is strongly subjective and laborious. To this end, a mathematically well-founded high-Re effects simulation method is proposed based on the response surface (RS) optimization algorithm in this article. Having the advantages of good considerations of random errors and simplified calculations using the polynomial models, RS method has been widely employed in chemical industry. However, it is seldom employed in physical experiments. Using a case study of Weisweiler cooling tower, it has been proved that model tests using the new high-Re effects simulation method based on RS optimization algorithm can objectively and easily reproduce the mean and the fluctuating wind pressure distributions measured on the spot, and the model-scale spectral characteristics of the wind pressures obtained by using the new high-Re effects simulation method agree well with the full-scale ones. Besides, numerical analyses undertaken on a computational fluid dynamics platform also indicate the validity of the new method.