An experimental-computational study of the crack opening displacement (COD) was performed to evaluate the ability of this parameter through the hysteresis loop area and energy release rate (ERR) to characterise fatigue crack growth under isothermal and thermomechanical conditions. To this end, a range of experimental crack growth tests were carried out including isothermal fatigue (IF), creep-fatigue interaction (CFI), in-phase (IP), and out-of-phase (OOP) thermomechanical fatigue (TMF). The crack growth experimental results in terms of COD and ERR were interpreted based on multi-physics finite element analyses of the stress–strain and displacement fields performed by incorporating Maxwell 3D, Fluent, and the transient structural modules of ANSYS. As a result of measurements and computations, the COD on the outer surface of the SENT specimen at the location of the original notch was found to be directly related to the crack tip opening displacement (CTOD). To gain insight into the fatigue crack growth mechanism operating under isothermal and TMF conditions, the fracture surfaces of all the tested specimens were examined using a scanning electron microscope to compare the morphology and changes in the dominant failure mechanisms. It was found that propagating cracks under isothermal and thermomechanical conditions interact with the microstructure of the material, and supporting fractography evidenced subtle differences in fracture mechanisms in terms of COD and ERR parameters. The relationship between the experimentally determined energy release rate and degradation function in the fatigue phase-field fracture methodology is discussed.