The full spectrum of herbicide resistance in a weed can vary according to the mechanistic basis and cannot be implied from the selective pressure. Common ragweed (Ambrosia artemisiifolia L.) is an important weed species of horticultural crops that has developed resistance to linuron based on either target site– or non–target site resistance mechanisms. The objective of the study is to characterize the cross-resistance to metribuzin of linuron-selected biotypes of A. artemisiifolia with target site– and non–target site resistance and determine its genetic basis. Crosses were made between two types of linuron-resistant biotype and a linuron-susceptible biotype, and the progeny were further backcrossed with susceptible plants to the third backcross (BC3) generation to determine their responses to both herbicides compared with parental lines. The target site–based linuron-resistant biotype was cross-resistant to metribuzin, and resistance to both herbicides was maintained at the same level in the BC3 line. In contrast, the linuron-selected biotype with a non–target site resistance mechanism was not cross-resistant to metribuzin. In addition, the BC3 lines deriving from the non–target site resistant parents had very low-level resistance. While the target site–resistance trait is maintained through multiple crosses, non–target site based resistance would be lost over time when selection is absent or insufficient to retain all genes involved in resistance as a complex trait. This would imply A. artemisiifolia biotypes with different mechanisms would need to be managed differently over time.