Rationale. Patient, brain-tumor, and brain-tumor-treatment factors may negatively impact brain tumor patients’ health-related quality of life (HRQOL) and executive functioning (EF). Yet, in order to inform clinical decisions, more information is needed about what factors influence HRQOL and EF, the trajectories of HRQOL and EF overtime, and potential causal relationships between HRQOL and EF. Methods. Adults with primary brain tumors (N = 53) were enrolled in a prospective, longitudinal study evaluating the effects of radiation therapy (RT) over the first year following RT. All patients completed a self-report measure of HRQOL and objective EF assessments at baseline (pre-RT), and three months, six months, and 12 months following RT. Descriptive statistics and general linear model regression with contrast coding were used to characterize HRQOL and EF at baseline based on patient factors, tumor factors, and treatment factors. Linear mixed effects models were used to examine the trajectories of HRQOL and EF over time, controlling for significant characteristics previously identified. Cross-lagged panel model path analysis was used to examine the interrelationships between HRQOL and EF over time. Results. Patients in this study were primarily middle-aged, married, well-educated White men and women. Seizures, steroid use, and future RT type were related to HRQOL at baseline. Marital status, seizures, tumor laterality, steroid use, antiepileptic drug use, and future chemotherapy use were related to EF at baseline. HRQOL did not exhibit a trend over time. EF exhibited a cubic trend over time. There was one statistically causal pathway between HRQOL and EF; EF performance at six-month follow-up was predictive of HRQOL at 12-month follow-up. Conclusions. Findings suggest that patients who receive steroids and experience seizures prior to RT and who have left-sided tumors may benefit from HRQOL and EF monitoring and possibly intervention. Additionally, there was complex pattern of change in EF over time, with early deleterious effects being followed by improvement. Patients’ EF six months after RT may impact their HRQOL one-year post-RT completion. Although the mechanisms underlying this relationship remain unclear, it is possible that interventions to improve or preserve EF prior to six-months post RT may facilitate later improvements in HRQOL.