Macrophages adopt a unique glycolytic metabolism, or immunometabolism, essential for the antimicrobial functions of these innate-immune cells. In this study, we observed that infection with the bacterial pathogen Legionella pneumophila (L. pn) degraded macrophage host mRNAs encoding enzymes required for glycolysis. By screening a library of L.pn mutant strains, we identified LegC4 as the “effector” protein essential for mRNA degradation and the suppression of host glycolysis. Using cross-linking immunoprecipitation (CLIP-seq), we demonstrated that LegC4 directly targeted glycolytic mRNAs by binding to a guanine (G)-rich RNA motif overrepresented within these transcripts. CryoEM structural analysis of an inactive mutant of LegC4 (LegC4H60A) in complex with its ssRNA substrate also revealed a non-canonical RNA-binding domain (RBD). This work is the first description of a bacterial effector that binds to eukaryotic host mRNA and has revealed an entirely novel mechanism for post-transcriptional regulation of glycolysis within the cell.