Isothermal (IF) and thermo-mechanical fatigue (TMF) tests were conducted on 316L welded joints to investigate the effects of phase angle (in-phase (IP), clockwise-diamond (CD), and out-of-phase (OP)) and mechanical strain amplitude (±0.4 %, ±0.5 %, ±0.6 %) on deformation and microregion fracture mechanisms. Results reveal that increasing strain amplitude induces a higher softening rate, reduced fatigue life, and more pronounced dynamic strain aging (DSA). Nevertheless, there is a complicated discrepancy in the cyclic deformation between various phase angles. At high strain amplitudes, local embrittlement along the austenite/δ-ferrite interface induces cracking in the weld metal (WM) under both IF and TMF loadings, with TMF life increasing with phase angle. At a lower strain amplitude of 0.4 %, however, fracture location migration and different TMF life were observed. Microstructural analysis reveals that during TMF a lower strain amplitude of 0.4 %, the microstructure in both base metal (BM) and WM evolves from simple planar structures to low-energy substructures, characterized by an increase in kernel average misorientation, geometrically necessary dislocations, and low-angle grain boundaries, together with a reduction in high-angle grain boundaries and twin boundaries. In the WM, increasing phase angle tends to reduce dislocation density and reproduces planar dislocation structures due to enhanced DSA, thereby lowering cellular structure maturity. Conversely, in the BM, dislocation proliferation and interaction intensify, enhancing cellular structure maturity and de-twinning effect, which reduces BM fracture resistance and causes fracture migration from the WM to the BM. Moreover, active DSA under CD loading improves deformation resistance in both microregions, prolonging fatigue life and contributing to the observed different TMF life.