The optimum design of tall buildings, which have a proportionately huge quantity of structural elements and a variety of design code constraints, is a very computationally expensive process. In this paper, a novel strategy, with a combination of evolutionary algorithms and machine learning methods, is developed for achieving the optimal design of tall buildings. The most time-consuming part is the analysis of tall buildings and the control of design code constraints requiring long and frequent analyses. The main idea is to use machine learning methods for this purpose. In this study, a practical methodology for obtaining the optimal design of tall building structures, regarding the constraints imposed by typical building codes, is introduced. The optimization process will be performed by a novel evolutionary algorithm, named asymmetric genetic algorithm (AGA), and in each iteration that requires checking the constraints for a large number of different structural states, machine learning methods, including MLP, GMDH and ANFIS-PSO are facilitators. More specifically, MLP (R2 = 0.988) has performed better than GMDH (R2 = 0.961) and ANFIS-PSO (R2 = 0.953). By coupling ETABS and MATLAB software, various combinations of sections for structural elements are assigned and analyzed automatically, thus creating a database for training neural networks. The applicability of the suggested procedure is described through the determination of the optimal seismic design for a 40-story framed tube building. Results designate that the present method not only supports the precision of the methodology but also remarkably diminishes the computational time and memory needed in comparison with the existing classical methods. More importantly, the optimization process time is also significantly decreased.