Abstract: Theory predicts that two-dimensional (2D) materials may only exist in the presence of out-of-plane deformations on atomic length scales, frequently referred to as ripples. While such ripples can be detected via electron microscopy, their direct observation via surface-based techniques and characterization in terms of interaction forces and energies remain limited, preventing an unambiguous study of their effect on mechanical characteristics, including but not limited to friction anisotropy. Here, we employ high-resolution atomic force microscopy to demonstrate the presence of atomic-scale ripples on supported samples of few-layer molybdenum disulfide (MoS2). Three-dimensional force/energy spectroscopy is utilized to study the effect of ripples on the interaction landscape. Friction force microscopy reveals multiple symmetries for friction anisotropy, explained by studying rippled sample areas as a function of scan size. Our experiments contribute to the continuing development of a rigorous understanding of the nanoscale mechanics of 2D materials.