North America is a large producer of beef and contains approximately 12% of the world’s cattle inventory. Feedlots are an integral part of modern cattle production in North America, producing a high-quality, wholesome protein food for humans. Cattle, during their final stage, are fed readily digestible high-energy density rations in feedlots. Cattle in feedlots are susceptible to certain zoonotic diseases that impact cattle health, growth performance, and carcass characteristics, as well as human health. Diseases are often transferred amongst pen-mates, but they can also originate from the environment and be spread by vectors or fomites. Pathogen carriage in the gastrointestinal tract of cattle often leads to direct or indirect contamination of foods and the feedlot environment. This leads to the recirculation of these pathogens that have fecal–oral transmission within a feedlot cattle population for an extended time. Salmonella, Shiga toxin-producing Escherichia coli, and Campylobacter are commonly associated with animal-derived foods and can be transferred to humans through several routes such as contact with infected cattle and the consumption of contaminated meat. Brucellosis, anthrax, and leptospirosis, significant but neglected zoonotic diseases with debilitating impacts on human and animal health, are also discussed.