The Canadian Integrated Program for Antimicrobial Resistance Surveillance describes a strong correlation (r = 0.9, p<0.0001) between ceftiofur-resistant Salmonella enterica serovar Heidelberg isolated from retail chicken and incidence of ceftiofur-resistant Salmonella serovar Heidelberg infections in humans across Canada. In Quebec, changes of ceftiofur resistance in chicken Salmonella Heidelberg and Escherichia coli isolates appear related to changing levels of ceftiofur use in hatcheries during the study period, from highest to lowest levels before and after a voluntary withdrawal, to increasing levels after reintroduction of use (62% to 7% to 20%, and 34% to 6% to 19%, respectively). These events provide evidence that ceftiofur use in chickens results in extended-spectrum cephalosporin resistance in bacteria from chicken and humans. To ensure the continued effectiveness of extended-spectrum cephalosporins for treating serious infections in humans, multidisciplinary efforts are needed to scrutinize and, where appropriate, limit use of ceftiofur in chicken production in Canada.