MS67 potently degraded WDR5 in a panel of MLL-r AML and PDAC cells with low-nanomolar DC50 and high Dmax values in a VHL, proteasome, WDR5, and time-dependent manner and was highly selective for WDR5 in MS-based global proteomics studies. Here, KMT2A is linked to acute myeloid leukemia.