Purpose: To investigate the performance of combined T2 mapping and T2 iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) in orbital tissues to predict the therapeutic efficacy of intravenous glucocorticoids (IVGCs) for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO). Method: Sixty-three active and moderate-to-severe TAO patients (responsive group, n = 35; unresponsive group, n = 28) who underwent orbital MRI before receiving IVGCs were retrospectively enrolled. Baseline clinical characteristics and imaging parameters were analyzed and compared between the two groups of different therapeutic efficacy. Binary logistic regression analysis was conducted to determine the independent predictors, the predictive performance of which was evaluated using receiver operating characteristic curve analysis. Results: The mean T2 relaxation time of extraocular muscle (EOM-T2RTmean) (P = 0.001), maximum T2RT of EOM (EOM-T2RTmax) (P = 0.001), mean water fraction of EOM (EOM-WFmean) (P < 0.001), maximum WF of EOM (EOM-WFmax) (P < 0.001) and exophthalmos (P = 0.007) were significantly higher in the responsive group than in the unresponsive group. EOM-T2RTmean (P < 0.001) and EOM-WFmax (P < 0.001) were determined as independent predictors for responsive patients with TAO in the multivariable analysis. Combining EOMT2RTmean > 77.1 and EOM-WFmax > 91.52 demonstrated optimal efficiency for prediction (area under the curve = 0.844) and optimal predictive sensitivity (77.1%). Setting EOM-WFmax > 91.52 achieved the optimal predictive specificity (89.3%). Conclusions: Pretherapeutic quantitative measurements, based on combining T2 mapping and T2 IDEAL in orbital tissues, are valuable for predicting IVGC treatment response in active and moderate-to-severe TAO. EOMT2RTmean and EOM-WFmax may become promising IVGC treatment response predictors.