<p>Under the action of a vehicle reciprocating load, the welded joints of steel bridges are prone to fatigue cracks, which seriously affect the service quality of structures and threaten operational safety. An accurate evaluation of fatigue performance is the basic premise for ensuring the safe operation. A novel fatigue life prediction method for key welded joints of steel bridges based on a fine macroscopic two-scale damage evolution model is proposed. A fine macroscopic two-scale damage evolution model is established based on the principles of continuum damage mechanics. Based on the fatigue test data of the welded joints, the parameters of the fine macroscopic two-scale damage evolution model were determined via inversion. Hence, a fatigue test of unequal-thickness butt welding joints of a steel bridge was conducted, and the fatigue failure characteristics were analyzed. The fatigue lives of butt-welded joints with varying thicknesses were predicted using fine- and macro-two-scale damage evolution models. The results showed that the damage life could be accurately estimated using the fine-macro two-scale damage evolution model. When combined with the damage evolution model to simulate the failure process, the simulated failure surface was consistent with the actual failure surface, indicating that the established damage evolution model effectively reflects the failure process. The relevant research results provide theoretical support for the evaluation and prediction of the fatigue properties of the complex structures and joints of steel bridges.</p>