Techniques are provided for detecting and distinguishing stroke and cardiac ischemia based on electrocardiac signals. In one example, the device senses atrial and ventricular signals within the patient along a set of unipolar sensing vectors and identifies certain morphological features within the signals such as PR intervals, ST intervals, QT intervals, T-waves, etc. The device detects changes, if any, within the morphological features such as significant shifts in ST interval elevation or an inversion in T-wave shape, which are indicative of stroke or cardiac ischemia. By selectively comparing changes detected along different unipolar sensing vectors, the device distinguishes or discriminates stroke from cardiac ischemia within the patient. The discrimination may be corroborated using various physiological and hemodynamic parameters. In some examples, the device further identifies the location of the ischemia within the heart. In still other examples, the device detects cardiac ischemia occurring during stroke.