Aminoglycosides are an important class of antimicrobial agents for the treatment of life-threatening bacterial infections. 16S rRNA methyltransferases are especially troublesome due to their wide target range and ability to confer high levels of resistance. In the United States, the National Antimicrobial Resistance Monitoring System (NARMS) monitored 18,281 non-Typhi Salmonella isolates from humans from 1996 to 2006. Two isolates displayed resistance to amikacin, gentamicin, and kanamycin. PCR screening for methyltransferase genes showed AM04864 (S. enterica serotype Stanley, 1999) was positive for armA, while AM23818 (S. enterica serotype Virchow, 2005) was positive for rmtC. Sequence analysis confirmed armA was identical to that in Acinetobacter baumannii and S. enterica serotype Oranienburg, located between tnpU and tnpD of Tn1548 transposon; rmtC was identical to that in Proteus mirabilis, with upstream ISEcp1. Previously, armA was only identified in A. baumannii in the US, and rmtC had not been observed in the US. The patient with the rmtC-positive isolate had traveled to India, suggesting the infection originated there. Identification of these methyltransferase genes among US human non-Typhi Salmonella isolates indicates a potential reservoir for these resistance mechanisms.