In this study, the performance of the automatic gas metal arc welding (GMAW) process in vacuum for similar and dissimilar joints of A353 and A516 steel plates with different thicknesses was intensively evaluated. Fracture of all vacuum-welded samples occurred in the heat-affected zone (HAZ) of A516 steel, highlighting the significant influence of HAZ microstructure and width on the cryogenic impact energy and strength of these joints. According to microscopic observations and impact tests, the fractures were fully ductile for notches in the weld and A353 HAZ, where dimples were observed on the fracture surfaces and the impact energy exceeded 50 J. This ductile behavior is particularly significant for notches in the weld due to the presence of a vacuum during welding prevents the formation of gas voids and oxide and hydride compounds that are normally the origin of cracks. However, for notches in the A516 HAZ, where the cleavage faces were observed on the fracture surfaces and the impact energy was less than 30 J, the fractures were quite brittle. For dissimilar vacuum-welded samples, the impact energy and fracture type for notches in the weld and A353 HAZ were nearly the same as those in similar A353 joints. However, for notches in the A516 HAZ, the impact energy and fracture type were close to those observed in the A516 joints. Yield strength and ultimate tensile strength (UTS) of A353-A353 non-vacuum-welded samples compared to vacuum-welded samples decreased by more than 78% and 40%, respectively. As well as, yield strengths and UTSs of A516-A516 non-vacuum samples compared to vacuum samples decreased by more than 34% and 4%, respectively. On the other side, the impact samples with a notch position in the weld suffered brittle fracture instead of ductile fracture because their impact energy decreased by about 40%.