This paper proposes the application of active multiple tuned mass dampers (AMTMD) for translational and torsional response control of a simplified two-degree-of-freedom (2DOF) structure, able to represent the dynamic characteristics of general asymmetric structures, under the ground acceleration. This 2DOF structure is a generalized 2DOF system of an asymmetric structure with predominant translational and torsional responses under earthquake excitations using the mode reduced-order method. Depending on the ratio of the torsional to the translational eigenfrequency, i.e. the torsional to translational frequency ratio (TTFR), of asymmetric structures, the following three cases can be distinguished: (1) torsionally flexible structures (TTFR < 1.0), (2) torsionally intermediate stiff structures (TTFR = 1.0), and (3) torsionally stiff structures (TTFR > 1.0). The even distribution of the AMTMD within the whole width and half width of the asymmetric structure, thus leading to three cases of installing the AMTMD (referred to as the AMTMD of case 1, AMTMD of case 2, AMTMD of case 3, respectively), is taken into account. In the present study, the criterion for searching the optimum parameters of the AMTMD is defined as the minimization of the minimum values of the maximum translational and torsional displacement dynamic magnification factors (DMF) of an asymmetric structure with the AMTMD. The criterion used for assessing the effectiveness of the AMTMD is selected as the ratio of the minimization of the minimum values of the maximum translational and torsional displacement DMF of the asymmetric structure with the AMTMD to the maximum translational and torsional displacement DMF of the asymmetric structure without the AMTMD. By resorting to these two criteria, a careful examination of the effects of the normalized eccentricity ratio (NER) on the effectiveness and robustness of the AMTMD are carried out in the mitigation of both the translational and torsional responses of the asymmetric structure. Likewise, the effectiveness of a single ATMD with the optimum positions is presented and compared with that of the AMTMD.