Activation of heterotrimeric G proteins by G protein-coupled receptors (GPCRs) requires large-scale opening of the G -helical domain (AHD) to expose the nucleotide-binding site and facilitate GDP-GTP exchange. While orthosteric ligands are known to modulate GPCR conformation and signaling efficacy, how these effects propagate to the G protein itself remains unclear. Using single-molecule fluorescence resonance energy transfer (smFRET) imaging, we monitored AHD motions in Gi proteins coupled to the -opioid receptor (OR) across a spectrum of ligand- and nucleotide-bound states. We find that receptor ligands differentially modulate these dynamics from over 70 angstrom away, with higher-efficacy agonists more effectively promoting transitions to an open, low-nucleotide-affinity conformation. These data also capture transient OR-Gi intermediates during nucleotide binding and suggest that -opioid ligand efficacy arises in part from allosteric control over G protein conformational equilibria that kinetically gate activation.