The harmonic reducer of the space drive mechanism is one of the critical components of the satellite remote sensing system and its reliability is always required strictly in practice. During the manufacturing and usage processes of the harmonic reducer, uncertainties are ubiquitous and performance degradation is inevitable, which is mainly caused by the wear between the meshed tooth surfaces. They influence the reliability of harmonic reducer. In this paper, a performance margin modeling and reliability analysis for harmonic reducer considering multi-source uncertainties and wear is proposed. Firstly, based on the functional principle and the influence of wear, the performance margin model is established using hysteresis and transmission errors as key performance parameters. Then multi-source uncertainties are analyzed and quantified, including manufacturing errors, uncertainties in operational and environmental conditions, and uncertainties in performance thresholds. Finally, the reliability model is constructed based on the performance margin. A case study of a harmonic reducer is applied and the reliability sensitivity analysis is implemented to show the practicability of the proposed method. The results show that the proposed method can provide some suggestions to the design and manufacturing phases of the harmonic reducer.