Invasive Salmonella infections in adults are commonly treated with fluoroquinolones, a critically important antimicrobial class. Historically, quinolone resistance was the result of chromosomal mutations, but plasmid‐mediated quinolone resistance (PMQR) has emerged and is increasingly being reported in Enterobacteriaceae worldwide. PMQR may facilitate the spread of quinolone resistance, lead to higher‐level quinolone resistance, and make infections harder to treat. To better understand the epidemiology of PMQR in non‐typhoidal Salmonella causing human infections in the United States, we looked at trends in quinolone resistance among isolates submitted to the Centers for Disease Control and Prevention. We reviewed demographic, exposure and outcome information for patients with isolates having a PMQR‐associated phenotype during 2008–2014 and tested isolates for quinolone resistance mechanisms. We found that PMQR is emerging among non‐typhoidal Salmonella causing human infections in the United States and that international travel, reptile and amphibian exposure, and food are likely sources of human infection.