Abstract: When CFRP plates are externally bonded to damaged steel bridge members under a not-fully-unloaded condition, strain lag may occur between the CFRP and the steel plate, thereby compromising the fatigue strengthening effectiveness. To investigate the fatigue crack-growth behavior and life-prediction method for preloaded damaged steel plates strengthened with externally bonded CFRP plates, fatigue tests were conducted on six groups of center-cracked steel plates strengthened with CFRP plates under different preload ratios. The effects of preload ratio on fatigue failure mode, fatigue life, and crack-propagation behavior were examined. The experimental results indicate that externally bonded CFRP plates can markedly extend the fatigue life of preloaded damaged steel plates. For steel plates with an initial crack length of 18 mm, the fatigue life of specimens strengthened with CFRP plates bonded on both sides increased by up to 20.3 times compared with unstrengthened specimens. As the preload ratio of the steel plate increased from 0% to 25%, 50%, 75%, and 100%, the post-strengthening fatigue life decreased from 588,700 cycles to 557,900, 519,100, 457,200, and 432,200 cycles, respectively, with a maximum reduction of 26.6%. Furthermore, considering the influence of CFRP strain lag induced by strengthening under preloading, a stress analysis was performed for CFRP-strengthened, preload center-cracked steel plates, and a calculation method for the stress intensity factor at the crack tip was proposed. Based on a modified Paris model that incorporates plasticity-induced crack closure, a fatigue life prediction model for CFRP-strengthened, center-cracked steel plates under preload was established. The prediction errors between the model and the test results were within 15%, demonstrating the applicability and reliability of the proposed model. The findings provide theoretical and practical guidance for the fatigue strengthening design of steel bridge structures using CFRP under preload conditions.