The tribological properties of two-dimensional (2D) atomic layers are quite different from three-dimensional continuum materials because of the unique mechanical responses of 2D layers. It is known that friction on graphene shows a remarkable decreasing behavior as the number of layers increases, which is caused by the puckering effect. On other graphene derivatives, such as graphene oxide (GO) or reduced graphene oxide (rGO), the thickness dependence of friction is important because of the possibilities for technical applications. In this report, we demonstrate unexpected layer-dependent friction behavior on GO and rGO layers. Friction force microscopy measurements show that nanoscale friction on GO does not depend on the number of layers; however, after reduction, friction on rGO shows an inverse thickness dependence compared with pristine graphene. We show that the friction on rGO is higher than that on SiO2 at low load, and that an interesting crossover behavior at higher load occurs because of the lower friction coefficient and higher adhesion of the rGO. We provide a relevant interpretation that explains the effect of thickness and chemical reduction on nanoscale friction.