Targeted protein degradation (TPD) has enabled elimination of disease-relevant proteins as a novel way to inhibit proteins rather than temporarily blocking them. Several TPD modalities including Lysosome-Targeting Chimera (LYTACs) and proteolysis-targeting chimeras (PROTACs) have targeted cytosolic and membrane proteins and, the first PROTAC has recently obtained FDA approval. G protein-coupled receptors (GPCRs) are largely untargeted for degradation.  Here, we use agonist-induced internalization, a universal GPCR feature, to steer receptor fate towards degradation. Using the adenosine A3 receptor (A3AR) as a prototypical GPCR, we designed and synthesized a library of Agonist-mediated proteolysis Targeting Chimeras (AgoTACs) employing an orthosteric A3AR agonist tethered to an E3 ligase ligand. AgoTACs LUF8132, and LUF8173 rapidly internalized and reduced cellular A3AR levels up to 20% via the lysosomal degradation pathway. AgoTACs offer new opportunities to advance GPCR drug discovery by directed reduction of receptor levels.