Nanocomposite materials have recently attracted great attention for their wide range of applications, such as in smart materials, flexible electronics, and deformation sensing applications. Such materials make it possible to combine a polymer with functional fillers. In this study, flexible artificial leathers, exhibiting insulating properties and containing 1.5 or 2wt.% of graphene oxide (GO) in the polyurethane (PU) layer, were electrically activated via CO2 laser irradiation to obtain conductive paths at the surface exposed to the laser beam. As the material retained its insulating properties out of the irradiation areas, the laser scribing method allowed, at least in principle, a printed circuit to be easily and quickly fabricated. Combining a variety of investigation methods, including scanning electron microscopy (SEM), optical profilometry, IR and Raman spectroscopies, and direct current (DC) and alternate current (AC) electrical measurements, the effects of the laser irradiation were investigated, and the so-obtained electrical properties of laser-activated GO/PU regions were elucidated to unveil their potential use in both static and dynamic mechanical conditions. In more detail, it was shown that under appropriate CO2 laser irradiation, GO sheets into the GO/PU layer were locally photoreduced to form reduced-GO (RGO) sheets. It was verified that the RGO sheets were entangled, forming an accumulation path on the surface directly exposed to the laser beam. As the laser process was performed along regular paths, these RGO sheets formed electrically conductive wires, which exhibited piezoresistive properties when exposed to mechanical deformations. It was also verified that such piezoresistive paths showed good reproducibility when subjected to small flexural stresses during cyclic testing conditions. In brief, laser-activated GO/PU artificial leathers may represent a new generation of metal-free materials for electrical transport applications of low-current signals and embedded deformation sensors.