The article, explores the fatigue performance of a high-manganese TWIP steel under low-cycle fatigue conditions. The researchers aimed to address a gap in the existing literature by systematically analysing the role of mechanical twinning in the fatigue resistance of TWIP steel under different strain regimes. Fatigue tests were conducted in three modes: oscillating strain (tension-compression), positive-only strain and negative-only strain. These tests were performed at various strain amplitudes ranging from 0.6% to 1.2%. Their results revealed pronounced asymmetry in fatigue behaviour. The steel exhibited optimal performance under compressive (negative) strain and suboptimal performance under tensile (positive) strain, indicating greater sensitivity to tension during cyclic loading. At lower strain amplitudes, the material exhibited extended stabilisation with minimal damage accumulation. At higher strain levels, cyclic hardening was observed, particularly under oscillating and positive strain conditions. Manson–Coffin analysis showed that strength properties dominated fatigue life under oscillating loading, whereas plastic deformation played a more significant role under unidirectional strain modes. Fractographic analysis confirmed the material’s high ductility, revealing classic ductile failure features such as dimples and striations across all test conditions. Microstructural observations revealed that twinning occurred uniformly at lower strains but became more localised and intense near fracture zones at higher strains. These areas also exhibited increased hardness, linking localised twinning activity to material strengthening during cyclic deformation.