In deepwater test condition, the riser–test pipe (tubing string) system (RTS) is subject to the vortex-induced effect on riser, flow-induced effect on test pipe and longitudinal/transverse coupling effect, which is prone to buckling deformation, fatigue fracture and friction perforation. To resolve this, the three-dimensional (3D) nonlinear vibration model of deepwater RTS is established using the micro-finite method, energy method and Hamilton variational principle. Based on the elastic–plastic contact collision theory, the nonlinear contact load calculation method between riser and test pipe is proposed. Compared with experimental measurement results, calculation results using the proposed vibration model in this study and the single tubing vibration model in our recent work, the correctness and effectiveness of the proposed vibration model of the deepwater RTS are verified. Meanwhile, the cumulative damage theory is used to establish the fatigue life prediction method of test pipe. Based on that, the influences of outflow velocity, internal flow velocity, significant wave height, as well as top tension coefficient on the fatigue life of test pipe are systematically analyzed. The results demonstrate that, first, with the increase in outflow velocity, the maximum alternating stress and the annual fatigue damage rate increased. The location where fatigue failure of the test pipe is easy to occur at the upper “one third” and the bottom of test pipe are easy to occur fatigue failure. Second, with the increase in internal flow velocity, the “one third damage effect” of the test pipe will decrease, and the “bottom damage effect” of the test pipe increased that needs the attention of field operators. Third, during field operation, it is necessary to properly configure the top tension coefficient so that there can be a certain relaxation between the riser and the test pipe, so as to cause transverse vibration and consume some axial energy and load. The study led to a theoretical method for safety evaluation and a practical approach for effectively improving the fatigue life of deepwater test pipe.