Background: High-grade glioma is a highly malignant primary tumor of the central nervous system characterized by a poor clinical prognosis. The regulatory mechanisms of astrocytes within its TME are not fully understood. This study aimed to investigate the gene expression profiles, functional remodeling, prognostic significance, and regulatory role of astrocytes in the immune microenvironment of HGG, thereby identifying novel molecular markers and therapeutic targets for the management of HGG. Methods: ScRNA-seq was conducted on tumor and peritumoral normal tissues from three patients diagnosed with World Health Organization grade III HGG. To characterize astrocyte properties in HGG, spatial transcriptome deconvolution, cell-cell communication analysis, and differential gene enrichment analysis were performed. WGCNA was applied to data from The Cancer Genome Atlas, while Venn intersection combined with LASSO Cox regression was utilized to identify prognostic core genes derived from astrocytes. To assess the prognostic value and immune regulatory function of the identified core genes, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, and CIBERSORT immune infiltration analysis were executed. Results: In HGG, the proportions of astrocytes, microglia, and tumor cells were significantly elevated, with astrocytes emerging as the predominant cell population within the TME and engaging in extensive signaling interactions with microglia. Astrocytes demonstrated a bidirectional functional remodeling characterized by metabolic activation and the inhibition of matrix interactions. A total of five prognostic core genes derived from astrocytes were identified, among which LTF, NOX4, and HSP90B1 served as independent prognostic risk factors. A risk score model based on these genes effectively differentiated survival outcomes for HGG patients. Furthermore, core genes NDUFB2, HSP90B1, and LITAF were found to regulate the infiltration and polarization of CD8+ T cells and M2 macrophages, thereby contributing to an immunosuppressive TME that facilitates the malignant progression of HGG. Conclusions: Astrocytes are crucial regulators of high-grade glioma HGG TME remodeling, exhibiting distinct functional changes and molecular mechanisms. The identified prognostic core genes derived from astrocytes may serve as potential molecular markers for assessing HGG prognosis and as candidate targets for astrocyte-targeted antitumor therapies, thereby offering new insights for precision treatment of HGG. Trial registration: Not applicable.