Acute myeloid leukemia (AML) refers to one of the most lethal blood malignancies worldwide. FLT3-ITD mutation is recognized as the most common one that predicted a poorer prognosis. There have been many prominent FLT3-ITD inhibitors approved by the FDA for clinical therapies. However, as impacted by undesirable off-target effects, differentiated metabolic issues, and clinical drug resistance problems, it remains challenging to discover alternative and promising solutions for treating FLT3-ITD<sup>+</sup> AML. In this study, dovitinib was chemically modified and converted into CRBN-recruiting PROTACs. Two active compounds were identified, which showed enhanced antiproliferative effects against FLT3-ITD<sup>+</sup> AML cells, both <i>in vitro</i> and <i>in vivo</i>. As demonstrated from further biological evaluation, the compounds could induce the degradation of the FLT3-ITD and KIT proteins in a ubiquitin-proteasome-dependent manner and completely block their downstream signaling pathway. The findings of this study would provide another promising strategy to develop novel therapies for FLT3-ITD<sup>+</sup> AML.