In order to meet the requirements of cross-domain flight and wide airspeed range, the next generation advanced aero engines generally select adjustable thermodynamic cycle schemes combining with high cycle parameter, which significantly rise the temperature rate suffered by hot section components. Considering that previous attempts of thermo-mechanical fatigue (TMF) tests have been extremely limited by the low temperature rates (normally below 10 °C/s), it is hard to estimate the life effects of high transient thermal-mechanical cycle. In this study, a load-controlled servo-electric high transient TMF testing rig has been set up to investigate the influence of thermal-mechanical loading rate. On the GH4169 specimen, with optimized induction coil and compressed air cooling configuration, a 100 °C/s level triangular wave heating and cooling rate was achieved in the range of 300–650 °C. In-phase (IP) TMF tests were conducted at 10, 50 and 100 °C/s with fully reversed mechanical loading (R = −1) of 700, 800 and 900 MPa, respectively. According to the tests, increases in loading rate improve the TMF life, especially when the mechanical load is low, such as 700 MPa. Fractography under different loading conditions reveals extensive transgranular fracture characteristics. Additionally, at low loading rates, rough fracture surfaces and few dimple-like features were easily observed. In comparison, fracture surfaces with high loading rates tend to be flatter and exhibit obvious fatigue striations.