Background Arterial arteriosclerosis and atherosclerosis reflect vascular disease, the subclinical detection of which allows opportunity for cardiovascular disease (CVD) prevention. Larger cohort studies simultaneously quantifying anatomic thoracic and abdominal aortic pathologic abnormalities are lacking in the literature. Purpose To investigate the association of aortic wall area (AWA) and atherosclerotic plaque presence and burden as measured on MRI scans with incident CVD in a community sample. Materials and Methods In this prospective cohort study, participants in the Framingham Heart Study Offspring Cohort without prevalent CVD underwent 1.5-T MRI (between 2002-2005) of the descending thoracic and abdominal aorta with electrocardiogram-gated axial T2-weighted black-blood acquisitions. The wall thickness of the thoracic aorta was measured at the pulmonary bifurcation level and used to calculate the AWA as the difference between cross-sectional vessel area and lumen area. For primary or secondary analyses, multivariable Cox proportional hazards regression models were used to examine the association of aortic MRI measures with risk of first-incident CVD events or stroke and coronary heart disease, respectively. Results In 1513 study participants (mean age, 64 years ± 9 [SD]; 842 women [56%]), 223 CVD events occurred during follow-up (median, 13.1 years), of which 97 were major events (myocardial infarction, ischemic stroke, or CVD death). In multivariable analysis, thoracic AWA and prevalent thoracic plaque were associated with incident CVD (hazard ratio [HR], 1.20 per SD unit [95% CI: 1.05, 1.37] [P = .006] and HR, 1.63 [95% CI: 1.12, 2.35] [P = .01], respectively). AWA and prevalent thoracic plaque were associated with increased hazards: 1.32 (95% CI: 1.07, 1.62; P = .01) and 2.20 (95% CI: 1.28, 3.79; P = .005), for stroke and coronary heart disease, respectively. Conclusion In middle-aged community-dwelling adults, thoracic aortic wall area (AWA), plaque prevalence, and plaque volumes measured with MRI were independently associated with incident cardiovascular disease, with AWA associated in particular with stroke, and plaque associated with coronary heart disease. Clinical trial registration no. NCT00041418 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Peshock in this issue.