Antiphospholipid syndrome (APS) is an acquired thrombotic disorder with major clinical implications in ischemic stroke, particularly among young adults and in case of cryptogenic stroke. Antiphospholipid antibodies (aPLs) substantially increase stroke risk through multiple prothrombotic mechanisms, including vascular endothelial dysfunction, platelet activation, and complement system dysregulation. Thrombotic risk stratification requires comprehensive assessment of antibody profiles (e.g., triple positivity or positivity lupus anticoagulant), coexisting systemic lupus erythematosus (SLE), and traditional cardiovascular risk factors. APS-associated ischemic stroke exhibits complex pathophysiology, mediated by hypercoagulability, cardioembolism, large artery atherosclerosis, or small vessel occlusion. However, the absence of specific clinical or imaging biomarkers, complicates early diagnosis. Additionally, APS-related stroke is associated with a high recurrent rate and poor prognosis. Current evidence supports long-term anticoagulation as the cornerstone of secondary prevention, while high-risk patients (e.g., those with triple-positive antibody profiles) may benefit from combined antiplatelet agents or immunosuppressive therapies. This review emphasizes the urgent need to enhance early recognition and diagnosis of APS-related stroke, refine risk stratification for recurrence, and advance mechanistic research to develop precision secondary prevention strategies that address the underlying pathogenesis, ultimately improving clinical outcomes.