The invention relates to a method for simultaneously detecting 15 antibiotics in aquaculture sediment by combining microwave extraction-solid phase extraction pretreatment with a liquid chromatography-mass spectrometry (LC-MS) technology. The method comprises the following steps: step (1) pretreating sediment samples, adding internal standard substances sulfamethoxazole-13C6, norfloxacin-D5, penicillin G potassium salt-D5, tetracycline-D6, olaquindox-D4, amoxicillin-13C6 and trimethoprim-D3 indicating a recovery rate, adding an acetonitrile-phosphate buffer solution for microwave extraction ofextraction liquid; step (2) performing solid phase extraction, enrichment and purification on target antibiotics; and step (3) quantitatively detecting 15 antibiotics of seven types in sediment witha liquid chromatograph/mass spectrometer. The method can simultaneously detect residues of 15 antibiotics containing 8 new antibiotics in the aquaculture sediment at a time by optimizing the internalstandard substances, screening appropriate pretreatment method and optimizing detection conditions, and has the advantages of high recovery rate, high sensitivity, high stability, low detection limit,more true and reliable detection results and the like.