A critical role of the Gβγ dimer in heterotrimeric G-protein signaling is to facilitate the engagement and activation of the Gα subunit by cell-surface G-protein-coupled receptors. However, high-resolution structural information of the connectivity between receptor and the Gβγ dimer has not previously been available. Here, we describe the structural determinants of Gβ1γ2 in complex with a C-terminal region of the parathyroid hormone receptor-1 (PTH1R) as obtained by X-ray crystallography. The structure reveals that several critical residues within PTH1R contact only Gβ residues located within the outer edge of WD1- and WD7-repeat segments of the Gβ toroid structure. These regions encompass a predicted membrane-facing region of Gβ thought to be oriented in a fashion that is accessible to the membrane-spanning receptor. Mutation of key receptor contact residues on Gβ1 leads to a selective loss of function in receptor/heterotrimer coupling while preserving Gβ1γ2 activation of the effector phospholipase-C β.