Fatigue damage is a cumulative process. The fatigue design of offshore structures requires long term wave data to calculate fatigue damage. However, the climate change may affect the long-term wave statistics and consequently affect the cumulative fatigue damage. This paper aims to project the trend of annual fatigue damage of offshore floating structures and to detect the climate change impact on the future fatigue damage by coupling a conventional fatigue design method with climate and wave models. Firstly, climate scenarios are selected to project the global radiative forcing level over decadal or century time scales. Secondly, climate models are used to simulate global or regional atmosphere circulations and to obtain the wind field data. Thirdly, wave conditions are simulated by coupling wind driven wave models to climate models. Fourthly, stress analysis and fatigue assessments are conducted to project the annual fatigue damage. At last, control simulations are carried out in order to identify the range of natural variability and to detect the human-induced change. A case study is presented for a Floating Production Storage and Offloading (FPSO) unit operating in the Sable field offshore South Africa. The results indicate that, in the Sable field, the significant wave height is considerably influenced by the human-induced climate change. However, when detecting its effect on the annual fatigue damage, this change induced by human activities is still partially masked by the dominant natural variability. In addition, both the significant wave height and the annual fatigue damage increase over century time-scales.