As one of the typical fatigue details of the steel box girders, the U-rib butt weld in the embedded sections of the steel bridge decks is prone to fatigue cracking under the repeated action of the wheel load, and it directly affects the safe operation and durability of the bridge structures. In order to explore the fatigue cracking characteristics of U-rib butt weld on the roof of the orthotropic steel bridge decks, this paper first established a local model of the steel bridge deck using finite element simulation, and studied the fatigue stress characteristics of the U-rib butt welds in the embedded sections. Then it designed four full-scale single U-rib specimens and carried out a fatigue performance analysis of the actual structure combing with fatigue test. On this basis, the modified main S-N curve suitable for fatigue life prediction of U-rib butt welds was proposed by the structural stress method, and the fatigue crack propagation behavior of weld detail was explored based on the extended finite element method (XFEM). The results show that the longitudinal influence range of U-rib butt weld stress under the wheel load is two cross-spacer spacing, and the lateral influence range is 1.5 U-rib spacing. The arc transition area is subjected to the greatest fatigue stress amplitude and high stress concentration, which becomes a potential fatigue vulnerable point. The fatigue cracks observed in the experiment all start at the arc transition and continue to extend to the bottom edge of the longitudinal rib and the web. Based on the evaluation of the nominal stress method, the average fatigue strength of the welds is 68 MPa, which is close to the 71 MPa specified in the European Code. Compared with the main S-N curve proposed based on the equivalent structural stress method, the modified main S-N curve proposed in this research is safer and more conservative for fatigue life prediction. The extended finite element method can effectively simulate the expansion behavior of U-rib butt welds. Both fatigue tests and XFEM results indicate that the fatigue crack propagation direction depends on the location of the initial defect. When the initial defect appears on the bottom plate, fatigue cracks tend to extend along the bottom plate; but when the initial defect is located on the web plate, fatigue cracks tend to extend along the web.