Understanding the frictional properties of nanostructured surfaces is important because of their increasing application in modern miniaturized devices. In this work, lateral force microscopy was used to study the frictional properties between an AFM nanotip and surfaces bearing well-defined nanodomes comprising densely packed prolate spheroids, of diameters ranging from tens to hundreds of nanometers. Our results show that the average lateral force varied linearly with applied load, as described by Amontons’ first law of friction, although no direct correlation between the sample topographic properties and their measured friction coefficients was identified. Furthermore, all the nanodomed textures exhibited pronounced oscillations in the shear traces, similar to the classic stick–slip behavior, under all the shear velocities and load regimes studied. That is, the nanotextured topography led to sustained frictional instabilities, effectively with no contact frictional sliding. The amplitude of the stick–slip oscillations, σf, was found to correlate with the topographic properties of the surfaces and scale linearly with the applied load. In line with the friction coefficient, we define the slope of this linear plot as the stick–slip amplitude coefficient (SSAC). We suggest that such stick–slip behaviors are characteristics of surfaces with nanotextures and that such local frictional instabilities have important implications to surface damage and wear. We thus propose that the shear characteristics of the nanodomed surfaces cannot be fully described by the framework of Amontons’ laws of friction and that additional parameters (e.g., σf and SSAC) are required, when their friction, lubrication, and wear properties are important considerations in related nanodevices.