The directness (uniqueness) of both reaction routes (mechanisms) and overall reactions is deduced from chemical thermodynamics. Namely, starting from general thermodynamic relations, the basic kinetic equation is shown to be identically transformed so as to be decomposable into a sum of contributions originating from a finite and unique set of reactions called response reactions (RERs). For a general chemical reaction system involving terminal species (reactants and products) and intermediates, the basic kinetic equation may be further partitioned into contributions coming from RERs involving only terminal species and those RERs involving at least one intermediate. When the intermediate are assumed to obey the quasi-steady state approximation, the contributions coming from the RERs involving at least one intermediate vanish. As a result, the basic kinetic equation may be presented as a sum of contributions coming from RERs involving only terminal species, i.e., overall RERs. This approach is shown to provide an adequate physicochemical basis of mechanisms and overall reactions as well as an effective algorithm of their enumeration.