Biological macromolecules in solution are surrounded by a hydration shell, whose structure differs from the structure of bulk solvent. In crowded cellular environments, hydration shells constitute a large fraction of the overall solvent. While the importance of the hydration shell for numerous biological functions such as molecular recognition or enzymatic activity is widely acknowledged, it is poorly understood how the hydration shell is regulated by macromolecular shape and surface composition, mostly because a quantitative readout of the overall hydration shell structure has been missing. We show that small-angle scattering (SAS) in solution using X-rays (SAXS) or neutrons (SANS) provide a protein-specific footprint of the protein hydration shell that enables quantitative comparison with molecular dynamics (MD) simulations. By means of explicit-solvent SAS predictions, we derived the effect of the hydration shell contrast relative to bulk on the radii of gyration Rg of five proteins using 18 combinations of protein force field and water model. By comparing computed Rg values from SAXS relative to SANS in D2O with consensus experimental data from a worldwide round-robin study, we found that several but not all force fields yield a hydration shell contrast in remarkable agreement with experimental data. The hydration shell contrast, as captured by Rg values, strongly depends on the protein charge and geometric shape, thus providing a protein-specific footprint of protein–water interactions and a novel observable for scrutinizing atomistic hydration shell models against experimental data.