Zearalenone, a nonsteroidal estrogenic mycotoxin mainly produced by Fusarium species, causes reproductive disorders and hyperestrogenic syndromes in animals and humans. The bacterial strain Bacillus velezensis ANSB01E, isolated from chicken cecal content, was capable of effectively degrading zearalenone in both liquid medium and mouldy corn. Moreover, Bacillus velezensis ANSB01E exhibited good antimicrobial activities against animal pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, and Salmonella spp. Genome-based analysis revealed the presence of genes coding peroxiredoxin and alpha/beta hydrolase in Bacillus velezensis ANSB01E, which may be involved in zearalenone degradation. The study on the genome provides insights into the zearalenone degradation mechanisms and advances the potential application of Bacillus velezensis ANSB01E in food and feed industry.