Of interest in this work is the quantification of uncertainty in fatigue damage of a top-tensioned riser (TTR) resulting from vortex-induced vibration (VIV). Using a distributed wake oscillator model in time-domain simulations of a riser in uniform current, followed by rainflow cycle-counting, fatigue damage is computed. A polynomial chaos expansion (PCE) representation of damage is derived that treats three wake oscillator model variables as direct stochastic input: (i) motion amplitude; (ii) the ratio of vortex-shedding frequency to riser natural frequency; and (iii) current velocity. Damage at different locations along the selected riser is assessed. Damage predictions, obtained using the efficient PCE framework, are compared against the more computationally expensive alternative that involves Monte Carlo Simulation (MCS). This study suggests that PCE offers a tractable, versatile and accurate option for VIV-related fatigue damage prediction.