For the application in heavy wall pressure vessels such as hydrocracking reactors in the petrochemical industry, creep-resistant 2.25Cr–1Mo-0.25V steel is usually joined via submerged-arc welding. To ensure a long service lifetime at elevated temperatures and high pressures, the steel plates and weldments must maintain a beneficial combination of toughness and creep strength for several years. One approach to adjust the weldments' mechanical properties is to perform a post-weld heat treatment (PWHT). This study is dedicated to the impact of the PWHT-temperature and -time on the complex interplay of microstructure, precipitates and mechanical properties of 2.25Cr–1Mo-0.25V weld metal. The mechanical testing showed that a higher PWHT-temperature increases the weld metal's impact toughness and ductility while simultaneously decreasing its strength and creep resistance. The high-resolution investigation with transmission electron microscopy and high-energy X-ray diffraction demonstrated that this is linked to accelerated recovery processes and severe coarsening of fine MX carbonitrides. At lower PHWT-temperatures, the absolute increase of the MX phase fraction during PWHT and the MX coarsening is less pronounced, allowing the MX carbonitrides to effectively contribute to precipitation hardening by maintaining their fine size. Besides MX carbonitrides, the weld metal consists of Cr-rich M7C3 and M23C6 as well as a substantial amount of Mo- and V-rich M2C carbides. The precipitate transformation sequence during PWHT was found to be M3C→M3C + MX + M7C3→M3C + MX + M7C3+M23C6+M2C→MX + M7C3+M23C6+M2C, whereas prolonged annealing times at higher PWHT-temperatures again lead to the dissolution of M7C3 in favor of MX. Display omitted •Besides M7C3, M23C6 and MX, heat-treated 2.25Cr–1Mo-0.25V weld metal also possesses a substantial amount of M2C carbides.•The heat treatment temperature is decisive for the MX and M2C fraction, as well as the MX/M2C-ratio.•The carbide transformation sequence in 2.25Cr–1Mo-0.25V weld metal at 690–720 °C is M3C .→ M3C + MX + M7C3 → M3C + MX + M7C3+M23C6+M2C → MX + M7C3+M23C6+M2C.•Prolonged PWHT at 705 and 720 °C causes dissolution of M7C3, which is related to an increase of the MX fraction.