Composting has been widely used to turn livestock manure into organic fertilizer. However, livestock manure contains various contaminants including antibiotics and antibiotic resistance genes (ARGs). Here we investigated the variation of antibiotic resistome and its influencing factors during a commercial livestock manure composting. The results showed that composting could effectively reduce the relative abundance of ARGs and mobile genic elements (MGEs). As the dominant phylum in the composting samples, the key potential bacterial host of ARGs were Actinobacteria such as Leucobacter, Mycobacterium and Thermomonosporaceae unclassified. Meanwhile, Legionella pneumophila, Staphylococcus saprophyticus, Haemophilus ducreyi and Siccibacter turicensis may be the key potential pathogenic host of ARGs because of their co-occurrence with ARG subtypes. Redundancy analysis showed that the dissipation of ARGs during composting was linked to various environmental factors such as moisture. Bacterial succession as well as profile of biocide and metal resistance genes (BMRGs) were the determinants which constructed the antibiotic resistome during manure composting. However, the residues of ARGs and pathogens in compost products may still pose risks to human and crops after fertilization.