Pork head meat may harbor Salmonella and contaminate other carcass by-products during harvest and fabrication. A large pork processing plant in the United States was sampled bimonthly for 11 months to determine the concentration, prevalence, seasonality, serotype diversity, and antimicrobial susceptibility of Salmonella enterica isolated from cheek meat and head trim of swine carcasses. Each collection consisted of 25 samples on two consecutive days in the morning and afternoon shifts, for a total of 100 cheek meat and 100 head trim samples each month. Tissues were cultured for Salmonella by using restrictive media and enrichment techniques, and a subset of isolates was serotyped, analyzed for antimicrobial susceptibility, and genome sequenced. Salmonella postenrichment prevalence did not differ (P = 0.20) between cheek meat (63%) and head trim (66%). Postenrichment prevalence differed (P < 0.05) by month (January, 94%; March, 80%; May, 54%; July, 59%; September, 47%; and November, 55%) and by processing shift (morning, 68%; afternoon, 62%). The subset (n = 618) of isolates selected for serotyping yielded 21 distinct serotypes: Typhimurium (49%), Infantis (10%), Heidelberg (8%), I 4,[5],12:i:- (8%), and 17 other types (≤5%). In total, 407 multidrug-resistant (MDR; resistance to three or more antibiotic classes) isolates were identified. There were 120 isolates that exhibited the penta-resistant ACSSuT phenotype. In addition, 113 isolates exhibited decreased susceptibility to ciprofloxacin (MIC ≥ 0.12 μg/mL). Resistance genes blaCARB, blaSHV, blaTEM, aac(6')-Ib-cr,qnrB, sul2, and dfrA were expressed in numerous MDR Salmonella isolates. The data herein suggest that pork products from the head, compared with data reported for carcasses, may have a relatively high prevalence of Salmonella with diverse serotypes and MDR.