In this research work, the optimal parameters of post welding heat treatment (PWHT) for 12Cr–1Mo Steel in the welding condition are determined. The PWHT aims to decrease δ-ferrite percentage in the interface of the heat-affected zone (HAZ) and partially melted zone (PMZ). The parameters of post welding heat treatment (time, temperature, and cooling media) are determined through statistical analysis of a full factorial design. These considered δ-ferrite percentage in the HAZ-PMZ interface as the response variable, as well as microhardness in the critical welding regions. Subsequently, a predictive equation of δ-ferrite percentage in the HAZ-PMZ interface was obtained after the post welding heat treatment using non-linear regression coefficients given by full factorial design. The interaction between time and cooling media was essential to improve the PWHT. Also, a high temperature in the PWHT produced a total decrease of δ-ferrite. These mechanisms were associated with the dissolution of forming elements of the primary δ -ferrite, such as Cr and Mo. The PWHT optimal parameters to eliminate δ-ferrite were the temperature of 860 °C with the following combinations of treatment time and cooling media: 1 h-air and 2 h-oil.