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 CRBN substrates and other type I PRMTs. It also effectively inhibited the growth of multiple cancer cell lines and exhibited a favorable pharmacokinetic profile. Molecular modeling suggests that the unique conformation of the PRMT1 dimerization arm promotes productive ternary complex formation with CRBN, providing a structural basis for selective PRMT1 degradation. Overall, this study demonstrates that compound 4 is a first-in-class PRMT1-targeting PROTAC degrader and highlights its value as a chemical tool for studying PRMT1 biology and its therapeutic potential in PRMT1-dependent cancers.