Nowadays, many engineers believe that hybrid structures with reinforced concrete central core walls and perimeter steel frames offer an economical method to develop the strength and stiffness required for seismic design. As a result, a variety of such structures have recently been applied in actual construction. However, the performance-based seismic design of such structures has not been investigated systematically. In the performance-based seismic design, quantifying the seismic damage of complete structures by damage indices is one of the fundamental issues. Four damage states and the final softening index at each state for high-rise hybrid structures are suggested firstly in this paper. Based on nonlinear dynamic analysis, the relation of the maximum inter-story drift, the main structural characteristics, and the final softening index is obtained. At the same time, the relation between the maximum inter-story drift and the maximum roof displacement over the height is also acquired. A double-variable index accounting for maximum deformation and cumulative energy is put forward based on the pushover analysis. Finally, a case study is conducted on a high-rise hybrid structure model tested on shaking table before to verify the suggested quantities of damage indices.