The fatigue crack growth (FCG) behaviour in a Ni-based turbine disc alloy with two grain sized variants, in a low solvus high refractory (LSHR) superalloy has been investigated under a range of temperatures (650–725°C) and environments (air and vacuum) with trapezoidal waveforms of 1:1:1:1 and 1:20:1:1 durations at an R=0.1. The results indicate that a coarse grained structure possesses better FCG resistance due to the enhanced slip reversibility promoted by planar slip as well as the reduction in grain boundary area. The fatigue performance of the LSHR superalloy is significantly degraded by the synergistic oxidation effect brought about by high temperature, oxidising environment and dwell at the peak load, associated with increasingly intergranular fracture features and secondary grain boundary cracking. Secondary cracks are observed to be blocked or deflected around primary γ′, carbides and borides, and their occurrence closely relates to the roughness of the fracture surface, FCG rate and grain boundary oxidation. The apparent activation energy technique provides a further insight into the underlying mechanism of the FCG under oxidation–creep–fatigue testing conditions, and confirms that oxidation fatigue is the dominant process contributing to the intergranular failure process. At high enough crack growth rates, at lower temperatures, cycle dependent crack growth processes can outstrip crack-tip oxidation processes.