Abstract: The microstructure of nickel-base single crystal superalloy undergoes coarsening and rafting during long service at high temperature. Microstructural evolution leads to mechanical degradation and affects the service life of aero engines. The present work studied low cycle fatigue (LCF) behavior of coarsened and rafted DD6 alloys by fatigue tests, fracture analysis and life modelling. Coarsened and rafted DD6 alloys were prepared through thermal exposure and pre-creep treatments, respectively. Isothermal LCF tests were carried out at 980 °C under strain control on the alloys with different microstructure states. It was found that the fatigue lives of the coarsened and rafted alloys reduced significantly compared with the virgin-state alloy. Fracture surfaces and longitudinal sections of the tested specimens were characterized by SEM and optical microscope. The effect of rafted structure on the LCF damage mechanism was revealed. It was found that the crack propagation path would be affected by the microstructure state. In the coarsened or rafted alloys, mode I microcracks would deflect from its propagation path early, develop along the crystallographic planes and thus lead to faster failure when compared with that in the virgin-state alloy. Based on the fabric tensor and tensor decomposition method, the microstructure was quantitatively characterized and the characteristic parameters of both γ-matrix phase and the γ'-strengthened phase were extracted for life modelling. A new microstructure-sensitive isothermal fatigue life prediction model was proposed. The effects of coarsening and rafting on life reduction were decoupled by correlating with the independent components of the fabric tensors of the γ-matrix phase and the γ'-strengthened phase, respectively. Under the new model, the influence of γ/γ' microstructure morphology on LCF was well described. The accuracy and conservatism of prediction results were significantly improved. This research can provide theory basis for the strength design and life assessment of nickel-base single crystal turbine blades in aero engines.