Coupled equations of the dynamic model and the Van der Pol wake oscillator model are solved by the central finite difference method for the deepwater drilling riser. The vortex-induced vibration (VIV) response and fatigue life of the riser are calculated and the model validation is performed by comparing with the published experimental and simulation results. The effects of the top tension, current flow velocity, flow velocity profile, internal flow velocity as well as the installation of buoyancy modules on the VIV are discussed. Dynamic response and fatigue life of the riser under In-Line (IL) and Cross-Flow (CF) VIV are preliminarily analyzed. The results show that the VIV of the riser has multiple modes and exhibits a mixed behavior of standing waves and traveling waves. With the increase of top tension and flow velocity profile coefficient, the order of the VIV dominant mode and the peak values of the root mean square (RMS) of VIV displacement decrease, and the fatigue life of the riser is extended. With the increase of current flow velocity, the order of the VIV dominant mode increases and the riser fatigue life decreases. The effect of internal flow velocity on the riser VIV is neglectable. The installation of buoyancy modules can improve the riser stress state and extend the fatigue life. Compared with the CF VIV model, the calculated minimum fatigue life of the riser is extended under the IL and CF coupled VIV model due to the decrease of bending moment and the changing position of fatigue weak point.