Purpose and background: Isocitrate dehydrogenase (IDH) mutation and O-6 methyl guanine methyl transferase (MGMT) methylation are surrogate biomarkers of improved survival in gliomas. This study aims at studying the ability of semantic magnetic resonance imaging (MRI) features to predict the IDH mutation status confirmed by the gold standard molecular tests. Methods: The MRI of 148 patients were reviewed for various imaging parameters based on the Visually AcceSAble Rembrandt Images (VASARI) study. Their IDH status was determined using immunohistochemistry (IHC). Fisher’s exact or chi-square tests for univariate and logistic regression for multivariate analysis were used. Results: Parameters such as mild and patchy enhancement, minimal edema, necrosis < 25%, presence of cysts, and less rCBV (relative cerebral blood volume) correlated with IDH mutation. The median age of IDH-mutant and IDH-wild patients were 34 years (IQR: 29–43) and 52 years (IQR: 45–59), respectively. Mild to moderate enhancement was observed in 15/19 IDH-mutant patients (79%), while 99/129 IDH-wildtype (77%) had severe enhancement (p-value <0.001). The volume of edema with respect to tumor volume distinguished IDH-mutants from wild phenotypes (peritumoral edema volume < tumor volume was associated with higher IDH-mutant phenotypes; p-value < 0.025). IDH-mutant patients had a median rCBV value of 1.8 (IQR: 1.4–2.0), while for IDH-wild phenotypes, it was 2.6 (IQR: 1.9–3.5) {p-value = 0.001}. On multivariate analysis, a cut-off of 25% necrosis was able to differentiate IDH-mutant from IDH-wildtype (p-value < 0.001), and a cut-off rCBV of 2.0 could differentiate IDH-mutant from IDH-wild phenotypes (p-value < 0.007). Conclusion: Semantic imaging features could reliably predict the IDH mutation status in high-grade gliomas. Presurgical prediction of IDH mutation status could help the treating oncologist to tailor the adjuvant therapy or use novel IDH inhibitors.