Ultra-processed foods (UPFs) are industrially manufactured products that contain several additives and may contain high levels of added sugar, fat, salt, or little whole food. They also represent an increasing percentage of the world's diet and are increasingly associated with the development of cardiovascular disease (CVD). The findings of several meta-analyses and extensive, population-based longitudinal studies suggest there is a dose-response relationship between UPF consumption and each of the following outcomes: CVD, stroke, and total CVD-related deaths. Some food additives, especially emulsifiers (like carboxymethylcellulose and mono- and diglycerides), preservatives (like carboxymethylcellulose and mono- and diglycerides), and artificial colors (like tartrazine and sunset yellow), have been proven to independently alter the gut microbiome, induce cellular oxidative stress, and enhance chronic low-level low-grade inflammation. A common mechanistic pathway involves activation of the nuclear factor kappa B family of transcription factors, which mediate the production of pro-inflammatory cytokines, induce endothelial dysfunction, and promote atherogenesis. Thus, reducing UPF serves as a modifiable target for CVD prevention, can be incorporated into dietary guidelines and food-labeling practices to influence public health policy.