Various BRAF kinase inhibitors were developed to treat cancers carrying the BRAF^V600E mutation. First-generation BRAF inhibitors could lead to paradoxical activation of the MAPK pathway, limiting their clinical usefulness. Here, we show the development of two series of BRAF^V600E-targeting PROTACs and demonstrate that the exchange of the inhibitor scaffold from vemurafenib to paradox-breaker ligands resulted in BRAF^V600E degraders that did not cause paradoxical ERK activation.