Few developing countries have foodborne pathogen surveillance systems, and none of these integrates data from humans, food, and animals. We describe the implementation of a 4-state, integrated food chain surveillance system (IFCS) for Salmonella spp. in Mexico. Significant findings were 1) high rates of meat contamination (21.3%–36.4%), 2) high rates of ceftriaxone-resistant S. Typhimurium in chicken, ill humans, and swine (77.3%, 66.3%, and 40.4% of S. Typhimurium T isolates, respectively), and 3) the emergence of ciprofloxacin resistance in S. Heidelberg (10.4%) and S. Typhimurium (1.7%) from swine. A strong association between Salmonella spp. contamination in beef and asymptomatic Salmonella spp. infection was only observed in the state with the lowest poverty level (Pearson r = 0.91, p<0.001). Pulsed-field gel electrophoresis analysis of 311 S. Typhimurium isolates showed 14 clusters with 102 human, retail meat, and food-animal isolates with indistinguishable patterns. An IFCS is technically and economically feasible in developing countries and can effectively identify major public health priorities.