In supercritical thermal power plant units, a dissimilar joining of heat-resistant Cr-Mo steels such as P91 and P22 is commonly employed for components like boiler headers, piping, and steam turbine casing to increase the flexibility in design and application and also to reduce the material costs. However, a dissimilar joining of these two steels with matching filler has been subjected to several issues like mismatch in coefficient of thermal expansion, diffusion of elements, and unmixed zone formation. In the present investigation, microstructure and mechanical behavior study was conducted for the welded joint of different grade Cr-Mo steel, i.e., P22/P91 for the as-welded (AW) and post-weld heat treatment (PWHT) condition. The dissimilar welded joint (DWJ) was produced using the multi-pass gas tungsten arc welding (GTAW) process with Ni-based superalloy filler Inconel 82. Microstructure observation showed the absence of any type of possible cracking in the weldments obtained by Inconel 82 filler; however, an inhomogeneity in microstructure was found along the weldments. After the PWHT, carbon diffusion across the interface of P22 steel and Inconel 82 weld metal occurred, which resulted in the formation of soft zone (SZ) and hard zone (HZ). The welds produced using Inconel 82 filler displayed tensile strength and impact toughness of 608 ± 3.5 MPa and 83 ± 4 J, respectively. After PWHT, tensile strength and Charpy impact toughness were 507 ± 8 MPa and 75 ± 3 J, respectively. The fracture of tensile-tested specimen had occurred in the weak P22 base region for both AW and PWHT conditions, which ensured that welded joint was safe for supercritical power plant applications. The longitudinal residual stress of 380 MPa and transverse residual stress of 400 MPa were measured in top region of the weld metal, while in the root region, magnitude of 130 and 185 MPa was measured in longitudinal and transverse directions, respectively. © 2022, ASM International.