Common waterhemp resistance to protoporphyrinogen oxidase (protox)-inhibiting herbicides was first reported in northeast Kansas in 2001. The objective of this research was to determine the inheritance characteristics of the protox-resistance trait. Resistant and susceptible common waterhemp were screened for resistance and inbred lines were developed using full-sib mating for three generations in the greenhouse. After the third generation, resistant and susceptible plants were crossed in a male and female reciprocal manner creating 57 F₁ (first generation) lines. A proportion of the F₁ progeny was screened for resistance and the remaining progeny were used to create F₂ (second generation) and backcross (BC) lines. Approximately 500, 400, and 1400 F₁, BC, and F₂ progeny, respectively, were treated with 105 g ha⁻¹ of lactofen when plants reached the 8-node growth stage. Visual injury ratings were determined at 14 days after treatment and based on a scale of 0 = no injury and 100 = mortality. A plant was considered to be resistant when visible injury was less than 50%. Approximately 91 and 93% of F₁ progeny from susceptible female × resistant male and resistant female × susceptible male crosses, respectively, were scored as being resistant. There was no evidence of reciprocal differences or segregation in the F₁ indicating the resistance trait is dominant and contained in the nucleus. F₂ progenies supported a 3:1 genetic ratio and BC progenies supported a 1:1 ratio using a Chi-squared goodness-of-fit test. These results indicate resistance to protox-inhibiting herbicides is determined by a major dominant nuclear gene.