To better reveal the inner fatigue deterioration mechanism of steel industrial plants and effectively protect the plants from brittle fractures, a fatigue prognosis analysis method was proposed. Multi-scale fatigue damage models were established based on the power balance principle at the cross-scale interface. The damage of the structures caused by existing defects was quantified. Fatigue damage evolution and mixed mode crack propagation of the vulnerable positions were analyzed. Fatigue prognosis results illustrated that the fatigue damage of the steel crane runway girder evolved slowly at the initial phase and accelerated rapidly at the final phase, which proved that the assessment results based on Miner’s law are too conservative. Fatigue failure more likely occurred at the weld joint between the spile and the end sealing plate of the steel crane runway girder. The studied fatigue crack grew rapidly when the length a reached 5 mm, in which some actions should be taken. The crack in the serious position had great influence on the fatigue performance of other vulnerable parts.