Laser irradiation has been recently used to tune the mechanical properties of metallic glasses (MGs). However, the mechanism for plasticity improvement by laser irradiation is still not completely clear and requires further investigation. In this study, nanosecond pulsed laser irradiation is applied on a Zr-based MG surface under various laser powers, scanning speeds, and numbers of irradiation cycles. Then, the mechanical properties of the as-cast and laser-irradiated MG surfaces are characterized by nanoindentation tests. In particular, the indentation hardness, load-depth curve, serrated flow, and residual indent morphology of the surfaces are compared. The results show that the nanosecond pulsed laser irradiation softens the irradiated regions; the effect of the irradiation is slightly dependent on the laser irradiation parameters, and especially the laser scanning speed. Furthermore, laser irradiation considerably affects serrated flows in the load-depth curve and shear bands on the top surface, denoting different plastic deformation characteristics compared with the non-irradiated sample. These differences could be rationalized in terms of laser irradiation-induced formation of pre-existing shear bands in the subsurface layer, as well as thermal effects. The present results are expected to enhance the general understanding of the effects of laser irradiation on the mechanical properties of MGs.