Protein arginine methyltransferase 1 (PRMT1) plays a critical role in cancer, yet current PRMT1 modulators lack selectivity and rely on enzymatic inhibition. Here, we developed first-in-class PRMT1-targeting PROTAC degrader compound 4, designed based on the pharmacophore of our previously developed PRMT1 inhibitor. Compound 4 potently induces PRMT1 degradation in a concentration-, time-, and proteasome-dependent manner and exhibits high selectivity, with no detectable degradation of other common...