During long-term environmental exposure, polychloroprene undergoes ageing. Throughout the process of thermo-oxidation, chemical degradation leads to crosslinking in the polychloroprene macromolecular network, inducing a significant change in mechanical properties. Among the various consequences of ageing on the properties, the reduction of fatigue lifetime is still poorly understood and needs more accurate prediction methods. This study presents a methodology to relate change in fatigue lifetime loss and network crosslinking during ageing. The material investigated is a carbon black-filled polychloroprene, subjected to more than 25 ageing conditions. Changes in network crosslink density, mechanical strain energy, and fatigue lifetime is experimentally measured. In the present study, a novel prediction strategy is proposed: it relies on the network strain energy density and convincingly describes fatigue loss. As the approach potentially extends to three-dimensional and/or multiaxial problems, it holds promise for addressing ageing-related issues in the analysis of elastomeric parts.