The D 2 dopamine receptor (DRD2) is a therapeutic target for Parkinson’s disease 1 and antipsychotic drugs 2 . DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine 3 , leading to stimulation of G i and inhibition of adenylyl cyclase. We used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G i complex reconstituted into a phospholipid membrane. The extracellular ligand binding site of DRD2 is remodeled in response to agonist binding, with conformational changes in extracellular loop 2 (ECL2), transmembrane domain 5 (TM5), TM6, and TM7 propagating to opening of the intracellular G i binding site. The DRD2-G i structure represents the first experimental model of a GPCR-G protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine sidechains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help inform the design of subtype-selective DRD2 ligands for multiple human CNS disorders.