Human skin provides both physical integrity and immunological protection from the external environment, using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combined advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantified 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe here the quantitative distribution of structural proteins, known and novel proteins specific to cellular subsets and those with specialized immunological funtions such as cytokines and chemokines. We anticipate this proteomic atlas of human skin will become an essential community resource for basic and translational research (www.skin.science).