Hybrid Laser-Arc Welding (HLAW) is a relatively new joining technique that combines advantages from both laser beam welding and arc welding. The interaction between laser beam and arc welding provides advantageous synergic effects, especially for thick joints. On the other hand, this interaction brings extra complexity to HLAW, limiting its acceptance in industry. Therefore, it is still necessary to elucidate some features of HLAW, such as the influence of parameters and consumables on the characteristics of the resulting joints. In the present study, the effects of welding gases (Ar + CO2 in different proportions) and filler metals (solid and flux-cored wires) on thick S355 structural steel joints are assessed. The best welds in terms of geometric characteristics, microstructures, and mechanical behavior were fabricated with high CO2 content welding gases and flux-cored welding wires. The use of flux-cored wires promoted higher penetration, lower hardness, and formation of acicular ferrite, avoiding the formation of martensite encountered in joints welded with solid wires. Moreover, the application of flux-cored wires could lead to cost savings in future applications, by reducing the laser power required to produce sound joints.