AbstractRal GTPases belong to the RAS superfamily, and they are directly activated by K‐RAS. The RalGEF pathway is one of the three major K‐RAS signaling pathways. Ral GTPases do not possess a cysteine nucleophile to develop a covalent inhibitor following the strategy that led to a K‐RAS G12C therapeutic agent. However, several cysteine amino acids exist on the surface of guanine exchange factors that activate Ral GTPases, such as Rgl2. Here, we screen a library of cysteine electrophile fragments to determine if covalent bond formation at one of the Rgl2 surface cysteines could inhibit Ral GTPase activation. We found several chloroacetamide and acrylamide fragments that inhibited Ral GTPase exchange by Rgl2. Site‐directed mutagenesis showed that covalent bond formation at Cys‐284, but not other cysteines, leads to inhibition of Ral activation by Rgl2. Follow‐up time‐ and concentration‐dependent studies of derivatives identified by substructure search of commercial libraries further confirmed Cys‐284 as the reaction site and identified the indoline fragments as the most promising series for further development. Cys‐284 is located outside of the Ral ⋅ Rgl2 interface on a loop that has several residues that come in direct contact with Ral GTPases. Our allosteric covalent fragment inhibitors provide a starting point for the development of small‐molecule covalent inhibitors to probe Ral GTPases in animal models.