Fatigue tests have been conducted on an advanced disc Ni-based superalloy (Low Solvus, High Refractory (LSHR) alloy) at 650 o C in air under three-point bend loading to investigate the role of orientation-dependent grain boundary oxidation in crack initiation and early propagation. It is found that crack initiation occurs mainly from bulged grain boundary oxides, and cracks then predominantly propagate along the oxidised grain boundaries. These bulged oxides are extremely enriched in Co and preferentially form at the boundaries between high and low Schmid factor grains which are inclined normal to the applied tensile stress direction. Meanwhile, relatively flat/thin Ni/Ti/Al-rich oxide complexes also form at other grain boundaries, but they appear to be much less detrimental in fatigue crack initiation and propagation compared with the grain boundary bulged Co-rich oxide complexes.