This study evaluated the impact of human cytomegalovirus (HCMV) infection on vascular inflammation and clinical characteristics in patients with coronary atherosclerotic heart disease (CHD). A total of 180 CHD patients with HCMV infection (research group) and 90 CHD patients without HCMV infection (control group) were enrolled. Serum levels of hs-CRP, TNF-α, IL-6, and Lp-PLA2 were measured, and clinical data were collected. The research group showed significantly higher inflammatory marker levels than controls (p < 0.05). Mean viral load was 4.58 ± 1.01 copies/mL, and high-load patients had higher marker levels than low-load patients (p < 0.05). Significant between-group differences were observed in CHD severity, number of diseased vessels, stenosis degree, cardiac function, angina grade, and carotid atherosclerosis (p < 0.05). HCMV viral load was positively correlated with all inflammatory markers and clinical severity indices (p < 0.05). These findings indicate that HCMV infection is associated with exacerbated vascular inflammation and worse CHD progression, suggesting the need for timely antiviral intervention.