The detailed characteristics of strokes at high altitudes in diverse nations have not been extensively studied. We retrospectively enrolled 892 cases of first-ever acute ischemic strokes at altitudes of 20, 2550, and 4200 m in China (697 cases from Penglai, 122 cases from Huzhu, and 73 cases from Yushu). Clinical data and brain images were analyzed. Ischemic strokes at high altitudes were characterized by younger ages (69.14 ± 11.10 vs. 64.44 ± 11.50 vs. 64.45 ± 14.03, p < 0.001) and larger infract volumes (8436.37 ± 29,615.07 mm³ vs. 17,213.16 ± 47,044.74 mm³ vs. 42,459 ± 84,529.83 mm³, p < 0.001). The atherosclerotic factors at high altitude, including diabetes mellitus (28.8% vs. 17.2% vs. 9.6%, p < 0.001), coronary heart disease (14.3% vs. 1.6% vs. 4.1%, p < 0.001), and hyperlipidemia (20.2% vs. 17.2% vs. 8.2%, p = 0.031), were significantly fewer than those in plain areas. Polycythemia and hemoglobin levels (138.22 ± 18.04 g/L vs. 172.87 ± 31.57 g/L vs. 171.81 ± 29.55 g/L, p < 0.001), diastolic pressure (89.98 ± 12.99 mmHg vs. 93.07 ± 17.79 mmHg vs. 95.44 ± 17.86 mmHg, p = 0.016), the percentage of hyperhomocysteinemia (13.6% in Penglai vs. 41.8% in Huzhu, p < 0.001), and the percentage of smoking (33.1% in Penglai vs. 50.0% in Huzhu, p = 0.023) were significantly elevated at high altitudes. We concluded that ischemic stroke occurred earlier and more severely in the Chinese plateau. While the atherosclerotic factors were not prominent, the primary prevention of strokes at high altitudes should emphasize anticoagulation, reducing diastolic pressure, adopting a healthy diet, and smoking cessation.