Liquid–liquid phase separation (LLPS) plays a key role in the compartmentalization of cells via the formation of biomolecular condensates. Here, we combined atomistic molecular dynamics (MD) simulations and terahertz (THz) spectroscopy to determine the solvent entropy contribution to the formation of condensates of the human eye lens protein γD-crystallin. The MD simulations reveal an entropy tug-of-war between water molecules that are released from the protein droplets and the ones that are retained within the condensates, two categories of water molecules that were also assigned spectroscopically. A recently developed THz calorimetry method enables a quantitative comparison of the experimental and computational entropy changes of the released water molecules. The strong correlation mutually validates the two approaches and opens the way to a detailed atomic-level understanding of the different driving forces underlying LLPS.