This study delves into the impact toughness of medium-thick (12 mm thick) titanium alloy joints crafted through a multi-layer, multi-pass welding technique that blends laser-arc (MIG) hybrid welding technology. Microstructural scrutiny, employing optical microscopy, SEM and TEM, unveils a consistent composition across weld passes, with prevailing α/α′ phases interspersed with some β phase, resulting in basket-weave structures primarily dominated by acicular α′ martensite. However, upper regions exhibit Widmanstatten microstructures, potentially undermining joint toughness. Hardness testing indicates higher values in cosmetic layers (~420 HV) compared to backing layers and bending tests manifest superior toughness in lower joint regions, attributed to smaller grain sizes induced by repetitive welding thermal cycles. Impact toughness assessment unveils diminished values in the weld metal (WM) compared to the heat-affected zone (HAZ) and base material (BM), amounting to 91.3% of the base metal’s absorption energy. This decrement is ascribed to heightened porosity in upper regions and variations in grain size and phase composition due to multi-layer, multi-pass welding. Microstructural analysis proximal to failure sites suggests one mechanism wherein crack propagation is impeded by the β phase at acute crack angles. In essence, this study not only underscores the practicality of laser-MIG hybrid welding for medium-thick TC4 alloy plates but also underscores the reliability of joint mechanical properties.