The land application of livestock manure has been widely acknowledged as a beneficial approach for nutrient recycling and environmental protection. However, the impact of residual antibiotics, a common contaminant of manure, on the degradation of organic compounds and nutrient release in Eutric Regosol is not well understood. Here, we studied, how oxytetracycline (OTC) and ciprofloxacin (CIP) affect the decomposition, microbial community structure, extracellular enzyme activities and nutrient release from cattle and pig manure using litterbag incubation experiments. Results showed that OTC and CIP greatly inhibited livestock manure decomposition, causing a decreased rate of carbon (28%–87%), nitrogen (15%–44%) and phosphorus (26%–43%) release. The relative abundance of gram-negative (G-) bacteria was reduced by 4.0%–13% while fungi increased by 7.0%–71% during a 28-day incubation period. Co-occurrence network analysis showed that antibiotic exposure disrupted microbial interactions, particularly among G- bacteria, G+ bacteria, and actinomycetes. These changes in microbial community structure and function resulted in decreased activity of urease, β-1,4-N-acetyl-glucosaminidase, alkaline protease, chitinase, and catalase, causing reduced decomposition and nutrient release in cattle and pig manures. These findings advance our understanding of decomposition and nutrient recycling from manure-contaminated antibiotics, which will help facilitate sustainable agricultural production and soil carbon sequestration.