In summary, we developed a thermo-mechanochemical methodology for the atom-efficient direct synthesis of amides. The new protocol involves grinding carboxylic acids and amines and avoids using activators and additives. The combination of mechanical and thermal activation enables amide bond formation in a quantitative fashion, which in the case of the studied systems occurs in the liquid phase. We observed and isolated the crystalline intermediates between the reactants that precede the formation of amides. In the case of 1 and 2, their ammonium carboxylate salts act as reaction intermediates. The critical step for quantitative formation of amides 5 and 9 is the elimination of water from the reaction mixtures.