To study the temperature dependent transition from Mode I to crystallographic cracking, fatigue crack propagation tests at room temperature, 300 °C and 450 °C, and crystal plasticity finite element analysis are conducted for a Ni-base single crystal superalloy by adopting compact specimens with four different crystallographic orientations. Through experimental examination, the stress intensity factor range (ΔKI) at the critical point of transition scatters for different crystallographic orientations and cannot explain the transition behavior. The slip plane for transition at different temperatures keeps the same. By crystal plasticity finite element assessment, the slip systems on the slip plane for transition are quite activated comparing with other slip systems. The distributions of the plastic shear strains along 12 slip systems at the critical point of transition exhibit the same pattern at different temperatures, which explains the slip plane for transition at different temperatures keeping the same. A damage parameter considering slip plane activity and normal stress on the slip plane can explain the transition regardless of crystallographic orientations. The damage parameter at the critical point of transition increases with the temperature, which indicates that the resistance for transition to crystallographic cracking increases with the temperature.