Objective Detecting dysthyroid optic neuropathy (DON) in the early stages is vital for clinical decision-making. The aim of this study was to determine the feasibility of using an optic-nerve-based radiomics nomogram on water-fat imaging for detecting DON. Methods This study included 104 orbits (83 in the training cohort) from 59 DON patients and 131 orbits (80 in the training cohort) from 69 thyroid-associated ophthalmopathy (TAO) without DON patients. Radiomic features were extracted from the optic-nerve T2-weighted water-fat images for each patient. Selected radiomics features were retrained to construct the radiomic signature model and calculate the radiomic score (Rad-score). The conventional MRI evaluation model was constructed based on apical crowding sign, optic-nerve stretching sign and muscle index. The radiomics nomogram model combining the Rad-score and conventional MRI evaluation factors was then developed. Predictive performance of the three models was assessed using ROC curves. Results Eight radiomics features from water-fat imaging were selected to build the radiomics signature. The radiomics nomogram (based on Rad-score, apical crowding sign and optic-nerve stretching sign) had superior diagnostic performance than did the conventional MRI evaluation model (AUC in the training set: 0.92 vs 0.80, the validation set:0.88 vs 0.75). Decision curve analysis confirmed the clinical usefulness of the radiomics nomogram. Conclusions This optic-nerve-based radiomics nomogram showed better diagnostic performance than conventional MRI evaluation for differentiating DON from TAO without DON. The changes of the optic-nerve itself may deserve more consideration in the clinical decision-making process.