Abstract Background Glioblastoma is the most common malignant brain tumor in adults. Non-invasive clinical parameters could play a crucial role in treatment planning and serve as predictors of patient survival. Our register-based real-life study aimed to investigate the prognostic value of presenting symptoms. Methods Data on presenting symptoms and survival, as well as known prognostic factors, were retrieved for all glioblastoma patients in Sweden registered in the Swedish Brain Tumor Registry between 2018 and 2021. The prognostic impact of different presenting symptoms was calculated using the Cox proportional hazard model. Results Data from 1458 adults with pathologically verified IDH wild-type glioblastoma were analyzed. Median survival time was 345 days. The 2-year survival rate was 21.5%. Registered presenting symptoms were focal neurological deficits, cognitive dysfunction, headache, epilepsy, signs of raised intracranial pressure, and cranial nerve symptoms, with some patients having multiple symptoms. Patients with initial cognitive dysfunction had significantly shorter survival than patients without; 265 days (245–285) vs. 409 days (365–453; P < .001). The reduced survival remained after Cox regression adjusting for known prognostic factors. Patients presenting with seizures and patients with headaches had significantly longer overall survival compared to patients without these symptoms, but the difference was not retained in multivariate analysis. Patients with cognitive deficits were less likely to have radical surgery and to receive extensive anti-neoplastic nonsurgical treatment. Conclusions This extensive real-life study reveals that initial cognitive impairment acts as an independent negative predictive factor for treatment decisions and adversely affects survival outcomes in glioblastoma patients.