This study aimed to investigate the effects of antibiotics on environmental factors, hydrolase activity, and microbial community during aerobic co-composting of food waste and sewage sludge. The results showed that 5 mg/kg of antibiotics decreased cellulase activity and increased lipase and proteinase activity, while 20 mg/kg of antibiotics also decreased cellulase activity and increased the contents of Zn, Cu, and Hg. The dominant bacterial genera of the four treatment groups were Enterococcus, Pseudomonas, Idiomarina, Lactobacillus, and Bacillus. The addition of antibiotics affected the succession of microbial community structure. Microbial communities treated with 5 mg/kg antibiotics had the highest in diversity, while those treated with 20 mg/kg antibiotics had the lowest in richness. Redundancy analysis (RDA) revealed that the pH and temperature were the most important environmental factors that affected microbial community succession, followed by total nitrogen and moisture content during co-composting of food waste and sewage sludge.