Fatigue reliability prediction of welded structures is mainly based on nominal stress or hot spot stress method, but there are some problems such as grid sensitivity and joint geometry dependence. The Master S-N curve method can solve these problems well, but the corresponding reliability model needs to be studied. In this paper, the fatigue reliability model of welded structures based on the Master S-N curve method is studied. Considering the randomness of life and the correlation of failure, a reliability model is proposed, which reduces the computational burden by establishing a median damage-random threshold rule. Taking the welded drive axle housing as an object, the system reliability is analyzed under the bench test condition, and verified by the experimental data. After the verification, this method is used to predict the reliability of the axle housing under variable amplitude loading collected in the test field, and the results are verified by Monte Carlo (MC) method. When the P-S-N curves are parallel, the model is accurate, which is the characteristic of the Master S-N curve method. This method only needs to input the median damage value of the weak part, which is easy to be applied. This method can speed up the reliability prediction cycle of welded structures, which is beneficial to product innovation and optimal design. Finally, an improved design scheme is proposed for the weak parts of welding, and the effects of welding leg width, welding depth, and closed weld on fatigue life are revealed.