Fire blight, caused by the bacterium Erwinia amylovora, represents a significant threat to apple (Malus domestica) production. Currently, only a limited number of genes effectively involved in resistance to E. amylovora have been identified. Seeking new resistance candidates, we focused on a multigene family encoding amaranthin-like lectins, which are highly upregulated following chemical elicitation by acibenzolar-S-methyl (ASM). These lectins are believed to contribute to downstream defense by promoting bacterial aggregation, which led to their designation as M. domestica agglutinins (MdAGG). When loss-of-function editions were introduced into MdAGG genes, the plant's ability to mount a fully effective defense response against fire blight upon ASM treatment was compromised, confirming the role of MdAGGs in fire blight resistance. Next, we coupled the pPPO16 promoter, endogenous to apple and known to be rapidly induced during E. amylovora infection, with the coding sequence of MdAGG10 to create apple lines with fire blight-inducible MdAGG10 expression. Early MdAGG10 expression in these lines significantly improved resistance to fire blight, and an additional ASM treatment further enhanced this resistance. In summary, we conclude that MdAGGs act as defense genes whose timely expression can provide effective resistance against E. amylovora.