Palmer amaranth (Amaranthus palmeri S. Watson) populations resistant to acetolactate synthase (ALS)-inhibiting herbicides and glyphosate are fairly common throughout the state of North Carolina (NC). This has led farm managers to rely more heavily on herbicides with other sites of action (SOA) for A. palmeri control, especially protoporphyrinogen oxidase and glutamine synthetase inhibitors. In the fall of 2016, seeds from A. palmeri populations were collected from the NC Coastal Plain, the state’s most prominent agricultural region. In separate experiments, plants with 2 to 4 leaves from the 110 populations were treated with field use rates of glyphosate, glufosinate-ammonium, fomesafen, mesotrione, or thifensulfuron-methyl. Percent visible control and survival were evaluated 3 wk after treatment. Survival frequencies were highest following glyphosate (99%) or thifensulfuron-methyl (96%) treatment. Known mutations conferring resistance to ALS inhibitors were found in populations surviving thifensulfuron-methyl application (Ala-122-Ser, Pro-197-Ser, Trp-574-Leu, and/or Ser-653-Asn), in addition to a new mutation (Ala-282-Asp) that requires further investigation. Forty-two populations had survivors after mesotrione application, with one population having 17% survival. Four populations survived fomesafen treatment, while none survived glufosinate. Dose–response studies showed an increase in fomesafen needed to kill 50% of two populations (LD50); however, these rates were far below the field use rate (less than 5 g ha−1). In two populations following mesotrione dose–response studies, a 2.4- to 3.3-fold increase was noted, with LD90 values approaching the field use rate (72.8 and 89.8 g ha−1). Screening of the progeny of individuals surviving mesotrione confirmed the presence of resistance alleles, as there were a higher number of survivors at the 1X rate compared with the parent population, confirming resistance to mesotrione. These data suggest A. palmeri resistant to chemistries other than glyphosate and thifensulfuron-methyl are present in NC, which highlights the need for weed management approaches to mitigate the evolution and spread of herbicide-resistant populations.