A cast nickel based superalloy M963 was coated by high-velocity oxy-fuel (HVOF) spraying process. The effect of HVOF MCrAlY coating on thermo-mechanical fatigue (TMF) and isothermal fatigue (IF) in M963 was studied to understand fatigue life and failure mechanisms in coated and uncoated M963 alloy. Two types of TMF tests, i.e. in-phase (IP) and out-of-phase (OP), were performed in temperature range of 450~900°C, and IF tests were conducted at 900°C. It was found that the coating had a detrimental effect on fatigue life under OP TMF, while a beneficial effect of the coating existed under IP TMF and IF. Crack initiation time in the coated specimen was shorter than that in the uncoated specimen and the former’s crack density was higher than the latter’s one under OP TMF. The relationship of deformation and fracture response with fatigue life was discussed based on microscopic analysis.