We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a U.S. cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20-39 years old (1,043 patients), 40-59 years old (4,503 patients), and >60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20-39 yr: HR = 6.41; 40-59 yr: HR = 4.84; >60 yr: HR = 5.06; cause-specific survival: 20-39 yr: HR = 5.87; 40-59 yr: HR = 4.01; >60 yr: HR = 3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.