Ample research effort has been oriented into developing damage indices with the aim of estimating in a reasonable manner the consequences, in terms of structural damage and deterioration, of severe plastic cycling. Although several studies have been devoted to calibrate damage indices for steel and reinforced concrete members; currently, there is a challenge to study and calibrate the use of such indices for the practical evaluation of complex structures. The aim of this paper is to introduce an energy-based damage index for multi-degree-of-freedom steel buildings that accounts explicitly for the effects of cumulative plastic deformation demands. The model has been developed by complementing the results obtained from experimental testing of steel members with those derived from analytical studies regarding the distribution of plastic demands on several steel frames designed according to the Mexico City Building Code. It is concluded that the approach discussed herein is a promising tool for practical structural evaluation of framed structures subjected to large energy demands.