This paper develops a new nonlinear model for active control of three-dimensional (3D) irregular building structures. Both geometrical and material nonlinearities with a neuro-controller training algorithm are applied to a multi-degree-of-freedom 3D system. Two dynamic assembling motions are considered simultaneously in the control model such as coupling between torsional and lateral responses of the structure and interaction between the structural system and the actuators. The proposed control system and training algorithm of the structural system are evaluated by simulating the responses of the structure under the El-Centro 1940 earthquake excitation. In the numerical example, the 3D three-story structure with linear and nonlinear stiffness is controlled by a trained neural network. The actuator dynamics, control time delay and incident angle of earthquake are also considered in the simulation. Results show that the proposed control algorithm for 3D buildings is effective in structural control.