The invention discloses a method for simultaneously detecting 12 typical antibiotics in sewage and sludge. The method comprises the following steps: freeze-drying the sludge, grinding the freeze-dried sludge, sieving the ground sludge, sampling the sieved sludge, adding a substitute, adding methanol and Na2EDTA-McIlvaine buffer solution, uniformly mixing all above materials, carrying out ultrasonic treatment, centrifuging the obtained mixture, extracting the above obtained supernatant, mixing supernatants obtained after repeated three-time extraction, adding ultrapure water to the obtained supernatant mixture to reach a constant volume, and adjusting the pH value of the obtained solution to 3.0; carrying out suction filtration on a water sample, diluting the filtered water sample with ultrapure water, adjusting the pH value of the diluted water sample to 3.0, adding the substitute and Na2EDTA.2H2O, and allowing the obtained mixture to stand for 1h; carrying out solid phase extraction by adopting an SAX-HLB series system, activating the SAX-HLB series system with methanol, ultrapure water and acidic ultrapure water, adding above finally-obtained samples to the column of the system, leaching the samples, and eluting the samples with methanol; and blowing obtained eluates with nitrogen, re-dissolving the dried eluates, and quantifying the antibiotics by using optimized liquid chromatography tandem mass spectrometry parameters. The method adopting an optimized ultrasonic extraction, solid phase extraction and liquid-mass liquid chromatography tandem mass spectrometry technology to realize effective extraction and accurate quantification of the antibiotics in complex matrixes, and can be widely applied to determine sewage and sludge samples.