This paper proposed a practical damage detection method for frame structures based on finite element model-updating techniques. An objective function is defined as minimizing the discrepancies between the experimental and analytical modal parameters (namely, natural frequencies and mode shapes), which is set as a nonlinear least-squares problem with bound constraints. Unlike the commonly used line-search methods, the trust-region approach, a simple yet very powerful concept for minimization, is employed in order to make the optimization process more robust and reliable. Noting the objective function may sometimes be underdetermined for complex structures due to a relatively larger number of potential damaged elements, this paper attempts to propose a simple and convenient solution by expanding the original objective function. Moreover, the relative weighting scheme between different parts in the objective function is also investigated. One numerical two-story portal frame structure and two laboratory-tested frame structures, including a simple three-story steel frame structure and a more complex frame structure with bolted joints, are all adopted to evaluate the efficiency of the proposed technique. Some important issues about the application of the proposed method are also discussed in this paper.