Flexibility-based indexes such as inter-story deflection and flexibility curvature are sensitive to structural damage as illustrated in the literature. However, most of current studies on the flexibility-based damage detection algorithms assume that structural mass is known during the flexibility identification. To overcome this shortcoming, a flexibility-based damage detection algorithm without requiring known structural mass is proposed. An advanced signal processing procedure is first adopted to identify structural flexibility with unknown mass, then two flexibility-based damage indexes, the Uniform Load Surface (ULS), and the ULS curvature, are calculated for structural damage detection. The benchmark structures provided by the IASC-ASCE Structural Health Monitoring Group are studied to verify the effectiveness of the proposed flexibility-based indexes for damage detection, in which both simulation data (Phase I benchmark study) and experiment data (Phase II benchmark study) are investigated.