Despite decades of study, the structural mechanisms underpinning agonist efficacy in pentameric ligand-gated ion channels remain poorly understood. Here, a combination of extensive equilibrium and dynamical-nonequilibrium molecular dynamics simulations was used to obtain a detailed description of the structural and dynamic changes induced within the human α4β2 nicotinic acetylcholine receptor by a full and a partial agonist, namely acetylcholine and nicotine, and map how these rearrangements propagate within this receptor. These simulations reveal how the agonists modulate the patterns associated with intra and inter-domain communication and the evolution of the agonist-specific structural rearrangements. For the first time, we show that full and partial agonists, although generally using similar routes for through-receptor signal transmission, induce different amplitudes of conformational rearrangements in key functional motifs, thus impacting the rates of signal propagation within the protein. The largest agonist-induced conformational differences are located in the Cys loop, loops C and α1-β1 in the α4 subunit, loops F and β1-β2 in the β2 subunit and in the extracellular selectivity filter.