Nicotinic acetylcholine receptors (nAChRs) are critical ligand-gated ion channels in the human nervous system. They are targets for various neurotoxins produced by algae, plants, and animals. While many structures of nAChRs bound by neurotoxins have been published, the binding mechanism of toxins to the nAChRs remains unclear. In this work, we have performed extensive Gaussian accelerated molecular dynamics simulations on several Aplysia californica nAChRs in complex with α-conotoxins, strychnine, and pinnatoxins, as well as human nAChRs in complex with α-bungarotoxin and α-conotoxin, to determine the binding and dissociation pathways of the toxins to the nAChRs and the associated effects. We uncovered two common binding and dissociation pathways shared by toxins and nAChRs. In the first binding pathway, the toxins diffused from the bulk solvent to bind a region near the extracellular pore before moving downwards along the nAChRs to the nAChR orthosteric pocket. The second binding pathway involved a direct diffusion of the toxins from the bulk solvent into the nAChR orthosteric pocket. The dissociation pathways were the reverse of the observed binding pathways. Notably, we determined that the electrostatically bipolar interactions between the nAChR orthosteric pocket and toxins provided an explanation for the common binding mode shared by diverse toxins.