Due to the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover new antibiotics. To address this challenge, we trained a deep neural network capable of predicting molecules with antibacterial activity. We performed predictions on multiple chemical libraries and discovered a molecule from the Drug Repurposing Hub—halicin—that is structurally divergent from conventional antibiotics and displays bactericidal activity against a wide phylogenetic spectrum of pathogens including Mycobacterium tuberculosis and carbapenem-resistant Enterobacteriaceae. Halicin also effectively treated Clostridioides difficile and pan-resistant Acinetobacter baumannii infections in murine models. Additionally, from a discrete set of 23 empirically tested predictions from >107 million molecules curated from the ZINC15 database, our model identified eight antibacterial compounds that are structurally distant from known antibiotics. This work highlights the utility of deep learning approaches to expand our antibiotic arsenal through the discovery of structurally distinct antibacterial molecules. Display omitted •A deep learning model is trained to predict antibiotics based on structure•Halicin is predicted as an antibacterial molecule from the Drug Repurposing Hub•Halicin shows broad-spectrum antibiotic activities in mice•More antibiotics with distinct structures are predicted from the ZINC15 database A trained deep neural network predicts antibiotic activity in molecules that are structurally different from known antibiotics, among which Halicin exhibits efficacy against broad-spectrum bacterial infections in mice.