BACKGROUND: Electric excitation initiates myocardial mechanical contraction and coordinates myocardial pumping. We hypothesized that ECG global electric heterogeneity (GEH) and its longitudinal changes are associated with cardiac structure and function. METHODS AND RESULTS: Participants from the ARIC study (Atherosclerosis Risk in Communities) (N=5114; 58% female; 22% blacks) with resting 12-lead ECGs (visits 1–5) and echocardiographic assessment of left ventricular (LV) ejection fraction, LV global longitudinal strain, LV mass index, LV end-diastolic volume index, and LV end-systolic volume index at visit 5 were included. Longitudinal analysis included ARIC participants (N=14609) with measured GEH at visits 1 to 4. GEH was quantified by spatial ventricular gradient, QRS-T angle, and sum absolute QRS-T integral. Cross-sectional and longitudinal regressions were adjusted for manifest and subclinical cardiovascular disease. Having 4 abnormal GEH parameters was associated with a 6.4% (95% confidence interval, 5.5–7.3) LV ejection fraction decline, a 24.2 g/m 2 (95% confidence interval, 21.5–26.9) increase in LV mass index, a 10.3 mL/m 2 (95% confidence interval, 8.9–11.7) increase in LV end-diastolic volume index, and a 7.8 mL/m 2 (95% confidence interval, 6.9–8.6) increase in LV end-systolic volume index. Altogether, clinical and ECG parameters accounted for approximately one third of LV volume and 20% of systolic function variability. The associations were significantly stronger in cardiovascular disease. Sum absolute QRS-T integral increased by 20 mV*ms for each 3-year period in participants who demonstrated LV dilatation at visit 5. Sudden cardiac death victims demonstrated rapid GEH worsening, whereas those with LV dysfunction demonstrated slow GEH worsening. Healthy aging was associated with a distinct pattern of spatial ventricular gradient azimuth decrement. CONCLUSIONS: GEH is a marker of subclinical abnormalities in cardiac structure and function.