Supramolecular chemistry is intimately linked to the dynamical interplay between intermolecular forces and intramolecular flexibility. Here, we studied the ultrafast equilibrium dynamics of a supramolecular hydrogen-bonded receptor-substrate complex, 18-crown-6 monohydrate, using Fourier transform infrared (FTIR) and two-dimensional infrared (2DIR) spectroscopy in combination with numerical simulations based on molecular mechanics, density functional theory, and transition state theory. The theoretical calculations suggest that the flexibility of the macrocyclic crown ether receptor is related to an ultrafast crankshaft isomerization occurring on a time scale of several picoseconds and that the OH stretching vibrations of the substrate can serve as internal probes for the receptor's flexibility. The importance of population transfer among the vibrational modes of a given binding motif and of chemical exchange between spectroscopically distinguishable binding motifs for shaping the two-dimensional infrared spectrum and its temporal evolution is discussed.