The prolonged thermal exposure with centrifugal load results in microstructural degradation, which ultimately leads to a reduction in the fatigue and creep resistance of the turbine blades. The present work proposes a multi-scale framework to estimate the life reduction of turbine blades, which combines a microstructural degradation model, a two-phase constitutive model, and a microstructure-dependent fatigue and creep life reduction model. The framework with multi-scale models is validated by a Single Crystal (SC) Ni-based superalloy at the microstructural length-scale and is then applied to calculate the microstructural degradation and the fatigue and creep life reduction of turbine blades under two specific service conditions. The simulation results and quantitative analysis show that the microstructural degradation and fatigue and creep life reduction of the turbine blade are heavily influenced by the variations in the proportion of the intermediate state, namely, the maximum rotor speed status, in the two specific service conditions. The intermediate state accelerates the microstructural degradation and leads to a reduction of the life, especially the effective fatigue life reserve due to the higher temperature and rotational speed than that of the 93% maximum rotor speed status marked as the reference state. The proposed multi-scale framework provides a capable approach to analyze the reduction of the fatigue and creep life for turbine blade induced by microstructural degradation, which can assist to determine a reasonable Time Between Overhaul (TBO) of the engine.