The activation of inert C( sp 3 )-H bonds by non-heme Fe enzymes plays a key role in metabolism, epigenetics, and signaling, while providing a powerful biocatalytic platform for the chemical synthesis of molecules with increased sp 3 complexity. In this context, Fe II /α-ketoglutarate-dependent radical halogenases represent a broadly interesting system, as they are uniquely capable of carrying out transfer of a diverse array of bound anions following C-H activation. Here, we provide the first experimental evidence that bifurcation of H-atom abstraction and radical rebound is driven both by the ability of a dynamic metal coordination sphere to reorganize as well as by a second-sphere hydrogen-bond network where only two residues (Asn224 and Ile151) are necessary and sufficient. The identification of this minimal motif provides a paradigm for understanding the evolution of catalytic plasticity in these enzymes and yields new insight into the design principles by which to expand their reaction scope.