Cardiovascular disease (CVD) is the leading cause of death in the United States, and diet plays an instrumental role in CVD development. Plant-based diets have been strongly tied to a reduction in CVD incidence. In contrast, animal food consumption may increase CVD risk. While increased serum low-density lipoprotein (LDL) cholesterol concentrations are an established risk factor which may partially explain the positive association with animal foods and CVD, numerous other biochemical factors are also at play. Thus, the aim of this review is to summarize the major cellular and molecular effects of animal food consumption in relation to CVD development. Animal-food-centered diets may (1) increase cardiovascular toll-like receptor (TLR) signaling, due to increased serum endotoxins and oxidized LDL cholesterol, (2) increase cardiovascular lipotoxicity, (3) increase renin-angiotensin system components and subsequent angiotensin II type-1 receptor (AT1R) signaling and (4) increase serum trimethylamine-N-oxide concentrations. These nutritionally mediated factors independently increase cardiovascular oxidative stress and inflammation and are all independently tied to CVD development. Public policy efforts should continue to advocate for the consumption of a mostly plant-based diet, with the minimization of animal-based foods.