The use of antibiotics in the livestock and poultry industries has raised significant concern about environmental and health problems. In light of this, accurate knowledge of antibiotic residues in livestock and poultry manure is important for pollution management and strategic decision-making at the national level. This study aims to provide a comprehensive report on antibiotic residues in livestock and poultry manure in China using the published data of 3751 livestock and poultry feces in 29 provincial-level units over the past 20 years. In this study, the overall status of antibiotic residues in livestock and poultry feces was analyzed by mathematical statistics. Moreover, the spatio-temporal variation characteristics were analyzed by spatial statistics, and the differences among livestock and poultry species were evaluated by subgroup analysis. The finding indicated that tetracyclines (TCs), quinolones (QLs), sulfonamides (SAs), and macrolides (MLs) were the most abundant residues in livestock and poultry manure. The spatial and temporal variation revealed that the overall trend of antibiotic residues decreased gradually, and the spatial distribution was primarily concentrated in the southeast of Hu Line, exhibiting a “northeast-southwest” distribution. The distribution range also decreased slightly, with the residues of tetracyclines (TCs), quinolones (QLs), sulfonamides (SAs), and pleuromutilins (PMs) showing a significant spatial hot spot. The center of gravity of antibiotic residue shifted to the southwest between 2003 and 2021. In comparison to cow and sheep manure, the tetracyclines (TCs), sulfonamides (SAs), and macrolides (MLs) in pig and chicken manure were higher. The results can serve as a reference for the control and reduction of antibiotic pollution in livestock and poultry manure, as well as the wise utilization of those resources and achieving goals for clean agriculture.