Cardiovascular (CV) and cerebrovascular (CBV) diseases are common in the elderly and cause severe damage, with high morbidity, disability, and mortality. Hypertension, as a risk factor for a variety of CV and CBV diseases, also affects many elderly patients. This study aimed to investigate the relationship between serum FGF21 and vWF expression and carotid atherosclerosis (CAS) in elderly patients with hypertension. We recruited 143 elderly hypertensive patients admitted to our hospital from July 2017 to November 2019 to this study, including 75 patients with comorbid CAS (the observation group, OG) and 68 patients without CAS (the control group, CG). Enzyme-linked immunosorbent assay (ELISA) was used to test serum expression levels of FGF21 and vWF; receiver operating characteristic (ROC) curves to evaluate the value of FGF21 and vWF in diagnosing CAS and predicting the 6-month prognosis in elderly hypertensive patients; Pearson’s correlation analysis to analyze the correlation of FGF21/vWF with the plaque thickness and stenosis area in hypertensive patients with CAS. The incidence of CV and CBV events was markedly higher in the high FGF21/vWF group than in the low FGF21/vWF group. Patients from OG were divided into the high FGF21/vWF group and the low FGF21/vWF group based on the median expression level of FGF21/vWF, then the incidence of cardiovascular (CV) and cerebrovascular (CBV) events was compared between the high and low expression groups. Serum levels of FGF21 and vWF were markedly higher in patients from OG than in patients from CG. Both FGF21 and vWF were in positive correlation with the plaque thickness and stenosis area in patients from OG. The area under the ROC curve (AUC) for diagnosing CAS was 0.790 by FGF21 and 0.807 by vWF; the AUC for predicting the occurrence of CV and CBV events was 0.771 by FGF21 and 0.754 by vWF. Serum levels of FGF21 and vWF are increased in elderly patients with hypertension and comorbid CAS, so they can be used for diagnosing CAS and predicting prognosis.