The effects of voltage and laser beam (spot) diameter on the penetration depth during laser beam welding in a representative nickel-chromium (Ni-Cr) dental alloy were the subject of this study. The cast alloy specimens were butted against each other and laser welded at their interface using various voltages (160-390 V) and spot diameters (0.2-1.8 mm) and a constant pulse duration of 10 ms. After welding, the laser beam penetration depths in the alloy were measured. The results were plotted and were statistically analyzed with a two-way ANOVA, employing voltage and spot diameter as the discriminating variables and using Holm-Sidak post hoc method (a = 0.05). The maximum penetration depth was 4.7 mm. The penetration depth increased as the spot diameter decreased at a fixed voltage and increased as the voltage increased at a fixed spot diameter. Varying the parameters of voltage and laser spot diameter significantly affected the depth of penetration of the dental cast Ni-Cr alloy. The penetration depth of laser-welded Ni-Cr dental alloys can be accurately adjusted based on the aforementioned results, leading to successfully joined/repaired dental restorations, saving manufacturing time, reducing final cost, and enhancing the longevity of dental prostheses.