Mooring systems are important structural components of very long floating bridges. They effectively limit the transverse motions of the bridge under environmental loads. They also add viscous hydrodynamic damping to the entire system. The safe and economical design of mooring systems is thus important but also challenging especially when the wave conditions are inhomogeneous. In this paper, a computational study is carried out to investigate the responses of the mooring lines for a 4.6 km long fjord crossing floating bridge accounting for inhomogeneous wave conditions. Based on the structural responses, this study also attempts to evaluate the fatigue damage in the mooring lines by using different fatigue analysis methods. The accuracy of the spectral methods is examined by comparison with the conventional rainflow cycle counting algorithm. Numerical studies are conducted to obtain an indication of the effect of various wave inhomogeneities on the fatigue damage in the mooring lines.