Significance Synthetic auxin herbicides intersect basic plant developmental biology and applied weed management. We investigated resistance to 2,4-D in the Australian weed Sisymbrium orientale (Indian hedge mustard). We identified a mechanism involving an in-frame 27-bp deletion in the degron tail of auxin coreceptor IAA2, one member of the gene family of Aux/IAA auxin co-receptors. We show that this deletion in IAA2 is a gain-of-function mutation that confers synthetic auxin resistance. This field-evolved mechanism of resistance to synthetic auxin herbicides confirms previous biochemical studies showing the role of the Aux/IAA degron tail in regulating Aux/IAA protein degradation upon auxin perception. The deletion mutation could be generated in crops using gene-editing approaches for cross-resistance to multiple synthetic auxin herbicides.