Manufacture of eco-friendly chrome-free leather is of great significance for realizing sustainable development of leather industry. Conventional tanning theory believes that it is impossible to convert raw hide to leather without the utilization of cross-linking agent (e.g., chrome salts) among collagen fibers in raw hide. Here, we developed a brand-new leather manufacture strategy that relied on the composite dehydration media enabled self-driven directional dehydration mechanism to accomplish chrome-free leather manufacture for the first time, rather than followed the classic cross-linking mechanism that has been obeyed for more than one century in leather industry. We demonstrated that the essence of leather making is to regulate the water content in raw hide rather than to form cross-linkage among collagen fibers. The composite dehydration media comprised of anhydrous ethanol and molecular sieves (3A activated zeolite powder) successfully guaranteed continuous self-driven directional dehydration of raw hide by establishing stable water concentration gradient between raw hide and ethanol, which significantly increased the dispersity of collagen fibers in raw hide (with the water content reduced from 56.07% to 5.20%), thus obtaining chrome-free leather that is more ecological than chrome-tanned leather due to the elimination of any tanning agent. The as-prepared chrome-free leather exhibited outstanding tear force (174.86 N), tensile strength (24.56 N mm−2), elongation at break (53.28%) and dry-thermal stability, superior to chrome-tanned leather. Notably, the used composite dehydration media was recyclable for chrome-free leather manufacture, therefore facilitating an environmentally benign leather manufacture process. Our investigations are expected to open up a new conceptual leather making strategy that is applicable for realizing substantial manufacture of eco-friendly leather.