Acute brain injury (ABI) is prevalent among patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) and significantly impact recovery. Early prediction of ABI could enable timely interventions to prevent adverse outcomes, but existing predictive methods remain suboptimal. This study aimed to enhance ABI prediction using machine learning (ML) models and high-temporal-resolution granular data. We retrospectively analyzed 355 VA-ECMO patients treated at Johns Hopkins Hospital (JHH) from 2016 to 2024, collecting over 3 million data points from the JHH Research Electronic Data Capture (REDCap) database, with an average of 80,000 data points per patient. Acute brain injury was defined as ischemic stroke, intracranial hemorrhage, hypoxic-ischemic brain injury, or seizure. Four ML models were used: Random Forest, Categorical Boosting, Adaptive Boosting, and Extreme Gradient Boosting. Among 355 patients (median age 59 years, 56.9% male), 13.5% developed ABI. The models achieved an optimal area under the receiver operating characteristic curve (AUROC) of 0.79, accuracy of 87%, sensitivity of 53%, specificity of 99%, and precision-recall (PR)-AUC of 0.47. Key predictors included high minimum values of systolic blood pressure and variability in on-ECMO pulse pressure. High-resolution granular data enhanced ML performance for ABI prediction. Future efforts should focus on integrating continuous data platforms to enable real-time monitoring and personalized care, optimizing patient outcomes.