This paper proposes a novel unsupervised damage detection approach based on a memetic algorithm that establishes the normal or undamaged condition of a structural system as data clusters through a global expectation-maximization technique, using only damage-sensitive features extracted from output-only vibration measurements. The health state is then discriminated by considering the Mahalanobis squared distance between the learned clusters and a new observation. The proposed approach is compared with state-of-the-art ones by taking into account real-world data sets from the Z-24 Bridge (Switzerland), where several damage scenarios were performed. The results indicated that the proposed approach can be applied in structural health monitoring applications where life safety, economic, and reliability issues are the most important motivations to consider.