The present research investigates the effects of different welding techniques, namely traditional metal inert gas (MIG), cold metal transfer (CMT), and fiber laser-MIG hybrid, on the microstructural and mechanical properties of joints between extruded EN AW 6181/6082-T6 and cast EN AC 42100-T6 aluminum alloys. These types of weld are very interesting for junctions of Al-alloys parts in the transportation field to promote the lightweight of a large scale chassis. The weld joints were characterized through various metallurgical methods including optical microscopy and hardness measurements to assess their microstructure and to individuate the nature of the intermetallics, their morphology, and distribution. The results allowed for the evaluation of the discrepancies between the welding technologies (MIG, CMT, fiber laser) on different aluminum alloys that represent an exhaustive range of possible joints of a frame. For this reason, both simple bar samples and real junctions of a prototype frame of a sports car were studied and, compared where possible. The study demonstrated the higher quality of innovative CMT and fiber laser-MIG hybrid welding than traditional MIG and the comparison between casting and extrusion techniques provide some inputs for future developments in the automotive field.