Prothrombin gene mutation (prothrombin thrombophilia) is an inherited disorder that increases the risk of venous thrombosis. However, limited data exist on the risk of arterial stroke in an at-risk population. Several meta-analyses report slightly increased risk in specific populations. We report a 10-year-old Hispanic girl who presented to the emergency department with a seizure. This seizure occurred five days after she tripped and fell without any initial associated symptoms. She had left-sided hemiparesis on physical examination after the seizure. Imaging revealed internal carotid artery (ICA) dissection with thrombus, right caudate nucleus and putamen infarcts, and ischemic penumbra. She subsequently had an endovascular thrombectomy of the right ICA with reperfusion. Genetic testing showed a prothrombin gene mutation (G20210A). Prothrombin gene mutation was the most likely explanation for her stroke in the absence of a significant risk factor for arterial thrombosis or an underlying hypercoagulable disorder. Further investigations are required to determine the risks and evaluate the correlation between prothrombin gene mutation and ischemic stroke in children.