The frictional behavior during manipulation of a single ZnO nanowire with a mass of about 18.7 ng placed horizontally on a Si wafer was examined using atomic force microscopy (AFM). The frictional force measured was in the range of 36.4 nN to 69.3 nN, which corresponded to extremely high friction coefficients of 242 and 462, respectively. However, when the adhesion force of the nanowire was considered, the friction coefficients were similar to the values typically encountered in macro-scale systems. During manipulation of the nanowire, both rolling and sliding motions were observed depending on the nanowire–Si frictional interaction. Unlike macro-scale systems, the difference between the frictional forces of rolling/sliding and pure sliding motions of the nanowire was not drastic.