The fatigue behavior of the 800H weld joint at the temperature of 800 °C was investigated, taking into account the effects of residual stress and microstructure. To model the residual stress in the welded joint, a finite element method was employed and its accuracy was verified using a hole drilling method, which was also used to study the evolution of residual stress during cutting and heating processes. Additionally, the weld region was characterized by measuring the distributions of elements and micro-hardness via energy dispersive X-ray spectroscopy and Vickers hardness tester. Fatigue lives, curves of displacement versus the number of cycles were obtained, and the fracture morphology was analyzed. The results reveal that the calculated residual stress in the weld region agrees well with the experimental results, and the transverse residual stress reduces in magnitude due to cutting and heating. Element distribution and micro-hardness exhibit obvious variations from the base metal to the weld metal. The micro-hardness has a minor effect on residual stress but a significant impact on local stress amplitudes at the weld toe. Furthermore, fatigue fractures primarily occur at the weld toe when the maximum cyclic stress exceeds 200 MPa, while the fracture location varies within the middle weld metal under smaller loads.