We leveraged 4,017 livestock metagenomes spanning 14 years, illuminated the health risks and global patterns of livestock resistomes as well as the prevalence of clinically critical ARGs. Our results demonstrate that livestock manure serves as a huge reservoir for both known and latent ARGs. We developed a novel risk-assessment framework by integrating mobility potential, clinical significance and host pathogenic relevance. This study yields a comprehensive catalog of livestock ARGs, including ARG sequences, ARG-carrying contigs and MAGs, which serves as a valuable resource for surveillance and antibiotic stewardship efforts.