The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1-weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected. Gene set enrichment analysis (GSEA), significant analysis of microarray, generalized linear models, and Least absolute shrinkage and selection operator algorithm were used to explore radiogenomic and prognostic signatures of AG patients. GSEA indicated that angiogenesis and epithelial-mesenchymal transition were significantly associated with post-CE. Genes driving immune system response, cell proliferation, and focal adhesions were also significantly enriched. Gene ontology of 237 differential genes indicated consistent results. A 48-gene signature for CE was identified in TCGA and validated in CGGA dataset (area under the curve = 0.9787). Furthermore, seven genes derived from the CE-specific signature could stratify AG patients into two subgroups based on overall survival time according to corresponding risk score. Comprehensive analysis of post-CE and genomic characteristics leads to a better understanding of radiology-pathology correlations. Our gene signature helps interpret the occurrence of radiological traits and predict clinical outcomes. Additionally, we found nine prognostic quantitative radiomic features of CE and investigated the underlying biological processes of them.