Glioblastoma (GBM) and Diffuse Midline Gliomas (DMG) are lethal, high-grade brain tumors (BT) representing major unmet clinical needs. We identified B7H3 as an optimal target antigen and engineered a novel, high affinity B7H3-targeting chimeric antigen receptor (CAR) T cell. This novel CAR exhibits robust antigen-specific cytolysis, expansion, and polyfunctional cytokine production, alongside minimal tonic signaling and preservation of a stem/naïve memory phenotype. A single administration achieved durable tumor control and long-term survival across multiple orthotopic GBM xenograft models. We identified upregulation of the T cell inhibitory ligands PD-L1 and PD-L2 as a mechanism of therapeutic resistance and subsequently engineered our CAR T cells to constitutively secrete a PD-1-blocking scFv. Concomitant locoregional PD-1 blockade augmented antitumor efficacy, driving enhanced intratumoral infiltration of the adoptively transferred T cells and improved effector function. Furthermore, we demonstrated that direct intrapontine administration of CAR T cells drastically improves therapeutic efficacy across distinct DMG models relative to both intracerebroventricular delivery and an established clinical competitor. Intrapontine delivery was associated with reduced peripheral inflammatory biomarkers while facilitating ultra-low CAR T cell dosing regimens. Collectively, optimizing B7H3-targeted CAR T cells via intrinsic PD-1 blockade or precise delivery yields a highly potent immunotherapeutic strategy for high-grade BT.