The allosteric modulation of G-protein-coupled receptors (GPCRs) by sodium ions has received significant attention as crystal structures of several receptors show Na ions bound to the inactive conformations at the conserved Asp . To date, structures from 24 families of GPCRs have been determined, though mechanistic insights into Na binding to the allosteric site are limited. We performed hundreds-of-microsecond long simulations of 18 GPCRs and elucidated their Na binding mechanism. In class A GPCRs, the Na ion binds to the conserved residue 2.50 whereas in class B receptors, it binds at 3.43b, 6.53b, and 7.49b. Using Markov state models, we obtained the free energy profiles and kinetics of Na binding to the allosteric site, which reveal a conserved mechanism of Na binding for GPCRs and show the residues that act as major barriers for ion diffusion. Furthermore, we also show that the Na ion can bind to GPCRs from the intracellular side when the allosteric site is inaccessible from the extracellular side.