Creep-resistant 2.25Cr-1Mo-0.25V steel is commonly applied in the petrochemical industry, e.g., for hydrocracking reactors with large dimensions and high wall thicknesses. For this purpose, submerged-arc welding is the preferred joining process. As these reactors are operated under creep conditions, the sheet material, as well as the weld seams, require a balanced relation between creep strength and toughness in order to guarantee a long service life. In CrMoV steel, the stability and size of the carbides and especially the fine carbonitrides are of major importance for its mechanical properties at room and at elevated temperatures. This study uses high-resolution methods combined with thermo-kinetic precipitation calculation to investigate the impact of multi-layer welding on the carbides and carbonitrides in the bainitic microstructure of 2.25Cr-1Mo-0.25V steel. Atom probe tomography and transmission electron microscopy revealed the presence of solely M3C carbides in the last non-reheated weld bead, whereas multiple reheating by the deposition of overlying weld beads causes the precipitation of nano-sized V- and Nb-rich carbonitrides. Apart from these fine carbonitrides also M3C and Cr-, Mo- and Mn-rich M7C3 carbides were detected in the reheated area of the multi-layer weld metal. In contrast to results from the thermo-kinetic calculations, MX carbonitrides precipitate during cooling after reheating but not directly during cooling after welding.