This paper seeks to probe temperature-moisture-mechanical coupling fatigue behaviours of screwed composite-steel joints by using experimental and numerical methods. Novel temperature-moisture-mechanical (TMM) coupling constitutive model, fatigue failure criterion and progressive fatigue damage algorithm (PFDA) are first devised for simulating fatigue failure mechanisms and modes and for predicting fatigue lives of single-lap screwed composite-metal joints (CMJs) in arbitrary temperature-moisture environment. In order to validate the presented model and algorithm, tension–tension fatigue tests are then conducted on the CMJs in four representative environments: low temperature of −40 °C and dry (LTD), room temperature of + 23 °C and dry (RTD), room temperature of + 23 °C and wet (RTW) and elevated temperature of + 55 °C and wet (ETW), respectively. Finally, the TMM coupling fatigue behaviors of the CMJs are analyzed and discussed from the experiments and progressive fatigue damage modelling, and predicted results agree well with experimental findings, demonstrating the feasible and practical usage of the proposed model.