PurposeGlioblastoma is associated with especially poor outcome in the elderly. It is unclear if patients aged≥80 years benefit from tumor-specific therapy as opposed to receiving best supportive care (BSC) only.MethodsPatients with IDH-wildtype glioblastoma (WHO 2021), aged≥80 years, and diagnosed by biopsy between 2010 and 2022 were included. Patient characteristics and clinical parameters were assessed. Uni- and multivariate analyses were performed.Results76 patients with a median age of 82 (range 80–89) and a median initial KPS of 80 (range 50–90) were included. Tumor-specific therapy was initiated in 52 patients (68%). 22 patients (29%) received temozolomide monotherapy, 23 patients (30%) were treated with radiotherapy (RT) alone and 7 patients (9%) received combination therapies. In 24 patients (32%), tumor-specific therapy was omitted in lieu of BSC. Overall survival (OS) was longer in patients receiving tumor-specific therapy (5.4 vs. 3.3 months, p < 0.001). Molecular stratification showed that the survival benefit was owed to patients with MGMT promoter methylation (MGMTpos) who received tumor-specific therapy as opposed to BSC (6.2 vs. 2.6 months, p < 0.001), especially to those with better clinical status and no initial polypharmacy. Patients with unmethylatedMGMTpromoter (MGMTneg) did not benefit from tumor-specific therapy (3.6 vs. 3.7 months, p = 0.18). In multivariate analyses, better clinical status andMGMTpromoter methylation were associated with prolonged survival (p < 0.01 and p = 0.01).ConclusionBenefit from tumor-specific treatment in patients with newly diagnosed glioblastoma aged≥80 years might be restricted toMGMTpos patients, especially to those with good clinical status and no polypharmacy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11060-023-04362-y.