Escherichia coli O157:H7 is responsible for foodborne poisoning, incriminating contaminated animal food and especially beef meat. This species can survive in the digestive tract, but, up to now, very few studies have considered its survival during the gastrointestinal digestion of meat. The present study aimed to investigate the survival of the pathogenic strain E. coli O157:H7 CM454 during the gastrointestinal digestion of ground beef meat and its interactions with meal components using a semidynamic digestive model. The CM454 strain in meat survived throughout digestion despite acidic pH (pH 2) and the presence of bile salts. The addition of nitrite and ascorbate in the digestion medium led to a decrease in strain survival. During digestion, a release of free iron was observed, which was accentuated in the presence of the CM454 strain. In addition, the strain modified the Fe2+/Fe3+ ratio, in favor of Fe2+ compared to the noninoculated meat sample. In the presence of nitrite, nitroso compounds such as nitrosamines, nitrosothiols, and nitrosylheme were formed. E. coli O157:H7 CM454 had no impact on N-nitrosation but seemed to decrease S-nitrosation and nitrosylation.