Microstructures of long-term serviced F12 steel exposed at 545 °C have been investigated by electron microscopes. The hardness of the material was measured to be correlated with the variation of the microstructures. Fatigue properties of the material with different running time were evaluated and analyzed. The experimental results show that the coarsening of the precipitated carbides along boundaries and the formation of subgrains accelerate the degradation of the long-term creep properties of the steel. Fatigue crack initiation threshold from a notch linearly deceases with increasing the running time due to the variation of the distribution and the shape of the precipitated carbides. The degradation mechanisms of the F12 steel during their long-term service at high temperature are discussed.