Escherichia coli (n = 1439), isolated from the feces of apparently healthy grow-finish pigs in 20 herds, were tested for susceptibility to 16 antimicrobials. Logistic regression models were developed for each resistance that was observed in more than 5% of the isolates. Each production phase's (suckling, nursery, grow-finish pigs or sows) antimicrobial exposure rate, through feed or water, was considered as a risk factor. Management variables were evaluated as potential confounders. Six resistance outcomes were associated with an antimicrobial use risk factor and four included exposures of pigs outside the grow-finish phase. In the case of sulfamethoxazole, the odds of resistance increased 2.3 times for every 100,000 pig-days of nursery pig exposure to sulfonamides. Thus, swine producers and veterinarians must be aware that antimicrobial use in pigs distant from market could have food safety repercussions. Five resistance outcomes were associated with exposure to an unrelated antimicrobial class. Most notably, the odds of sulfamethoxazole and chloramphenicol resistance were each six times higher in herds reporting high (more than 500/1,000 pig-days) grow-finish pig, macrolide exposure compared to herds with no macrolide use in grow-finish pigs. Therefore, the potential for co-selection should be considered in antimicrobial use decisions. This study emphasizes the importance of judicious antimicrobial use in pork production.