Signal propagation in biological systems occurs through a series of inter- and intramolecular events, the precise pathways of which remain elusive in most cases. With respect to protein--DNA interactions in particular, little is known about the association and dissociation reaction pathways. Here we show that the exchange of amide protons detected by NMR can be used to characterize, at residue level, the mechanism, kinetics and thermodynamics of Lac headpiece (HP) interaction with DNA operators. Specific protein--DNA contacts responsible for the direct readout of the sequence are formed and broken at distinct time scales. Unfolding of the hinge helices triggers protein--DNA dissociation by progressive destabilization of distinct structural units, which is facilitated by the low stability of the protein in the uncomplexed state. Upon DNA binding, a dramatic alteration in the dynamics of the protein is observed, which may be used advantageously by the biological system to switch between functional states. Hydrogen-deuterium exchange can provide an unusually detailed view of the interaction mechanism of a protein--DNA complex and the associated energetics of DNA recognition with residue-level specificity.