Mucins are the macromolecular key components of mucus. On wet epithelia of mammals, mucin solutions and gels act as powerful biolubricants and reduce friction and wear by generating a sacrificial layer and establishing hydration lubrication. Yet the structure–function relationship of mucin adhesion and lubrication remains elusive. We study the adhesion behavior of mucin using atomic force microscopy-based single molecule force spectroscopy with covalently attached, lab-purified salivary MUC5B and gastric MUC5AC. We can resolve the structural motifs mediating adhesion on chemically distinct substrates, such as highly oriented pyrolytic graphite and steel. We report on force-induced partial unfolding of the von Willebrand factor type D like domains and deliver their unfolding rates and free energy barriers. These domains serve to dissipate energy during the desorption process of mucins. Partial mucin unfolding might significantly contribute to the stability of a sacrificial mucin layer during shearing processes, enhancing the lubrication potential of mucin solutions.