Amide proton transfer-weighted magnetic resonance imaging (APTw-MRI), which is effective in tumor characterization, has expanded its role in the head and neck. We aimed to evaluate the diagnostic ability of APTw-MRI in differentiating malignant from benign major salivary gland tumors compared with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE)-MRI. Between December 2017 and November 2018, 38 subjects, who were diagnosed with major salivary gland tumors and who underwent preoperative 3 T MRI, including APTw-MRI, DWI, and DCE-MRI, were included in this retrospective study. Twenty-three subjects had benign tumors, and fifteen had malignancies. APTw-signals of the tumors were measured and compared according to the histopathological diagnosis. Using receiver operating characteristic curve analysis, diagnostic performance of APTw-MRI was evaluated and compared with DWI and DCE-MRI using DeLong test. The maximum, mean, and median APTw-signals were significantly higher in malignant than in benign tumors (P < 0.001). The mean and maximum APTw-signals showed excellent area under the curve for predicting malignant tumors (0.948 and 0.939), which were significantly higher than the combining use of DWI and DCE-MRI (0.780) (P = 0.021 and 0.028). Therefore, APTw-MRI could be a useful tool for differentiating malignant from benign major salivary gland tumors, and can be applicable in the clinical setting.