It is generally expected that, in the case of multiple herbicide resistance, different resistance mechanisms within a weed will follow Mendel’s law of independent assortment. Research was conducted to investigate anecdotal observations suggesting that target site–based resistances to inhibitors of acetolactate synthase (ALS) and protoporphyrinogen oxidase (PPO) did not follow independent assortment in common waterhemp. Cosegregation of the two resistances was observed in backcross lines (population sensitive to both herbicides as recurrent parent). Specifically, whereas 52% of backcross plants were resistant to a PPO inhibitor, this percentage increased to 92% when the backcross plants were preselected for resistance to an ALS inhibitor. Molecular marker analysis confirmed that the corresponding genes (ALS and PPX2) were genetically linked. When data from all plants analyzed were pooled, the genetic distance between the two genes was calculated to be 7.5 cM. The two genes were found to be about 195 kb apart in the recently published grain amaranth genome, explaining the observed genetic linkage. There is likely enough recombination that occurs between the linked genes to prevent the linkage from having significant implications in terms of resistance evolution. Nevertheless, documentation of the happenstance linkage between target-site genes for resistance to ALS and PPO inhibitors in waterhemp is a reminder that one should not assume distinct resistance mechanism will independently assort.