Fatigue life tests of different plate thicknesses and penetration degrees were carried out for load-bearing cross-shaped welded joints. The fatigue results show a significant “thickness effect”. The fatigue limit of the 25 mm-thick fatigue specimen is 13.4% lower than that of the 16mm-thick fatigue specimen; the fatigue life of the weld toe has basically no difference with the change of penetration degree. Plate thickness is a key factor affecting fatigue life, and the thickness effect is jointly determined by the stress gradient along the plate thickness and the degree of surface stress concentration. The correction result based on the effective notch stress method is more accurate than the thickness correction formula in the ABS standard. The thickness effect produced by the load-bearing cross-shaped welded joint is evaluated by the thickness correction formula too low, which will bring a certain risk. The penetration ratio a/t affects the fatigue failure position of the load-bearing cross-shaped welded joint. The fatigue design of the load-bearing cross-shaped welded joint can be carried out by appropriately increasing the degree of penetration while satisfying the failure at the weld toe.