Radiotherapy remains the cornerstone treatment for primary brain tumors and brain metastases, largely due to the limited ability of chemotherapeutic agents to achieve therapeutic concentrations in the brain parenchyma. However, clinical studies consistently report that patients frequently develop severe neurotoxic sequelae during the late phases postradiotherapy, with cognitive impairment emerging as the most debilitating complication. This decline in neurocognitive function profoundly impacts patients’ quality of life and long-term prognosis. Despite decades of research into radiation-induced cognitive impairment, the precise molecular and cellular mechanisms driving this pathology remain poorly understood, posing a major barrier to effective prevention and treatment strategies. Historically, investigations into radiation-induced cognitive impairment have focused on late-stage, irreversible neurodegenerative changes. Recent advances in neuroimaging and functional assessment techniques, however, have uncovered subtle yet significant structural and functional disturbances in the central nervous system (CNS) during the acute and subacute post-irradiation phases. These early alterations— including microvascular injury, neuroinflammation, and synaptic dysfunction—may initiate cascades of chronic pathological processes that culminate in irreversible late-stage cognitive deficits. This paradigm shift underscores the critical need to elucidate the interplay between acute radiation injury and chronic neurodegeneration. In this review, we synthesize current knowledge on: 1) Acute CNS injury responses to radiation, including oxidative stress, blood-brain barrier disruption, and glial activation. 2) Structural and functional remodeling of neural circuits, such as hippocampal neurogenesis suppression and white matter tract degeneration. 3) Mechanistic links between early cellular damage and late cognitive decline, focusing on neuroimmune crosstalk and epigenetic dysregulation. Furthermore, we highlight recent breakthroughs in therapeutic development, including small-molecule inhibitors targeting neuroinflammatory pathways (e.g., TGF-β, NLRP3 inflammasome), antioxidants to mitigate oxidative stress, and neurotrophic factors to promote neural repair. By bridging preclinical mechanistic insights with translational opportunities, this analysis aims to advance both the biological understanding and clinical management of radiation-induced cognitive impairment.