Shattercane is a problematic summer annual grass weed species in regions that produce grain sorghum. Three shattercane populations (DC8, GH4, and PL8) collected from sorghum fields from northwestern Kansas survived the field-use rate (52 g ha−1) of postemergence-applied imazamox. The main objectives of this research were to 1) confirm and characterize the level of resistance to imazamox in putative imazamox-resistant (IMI-R) shattercane populations, 2) investigate the underlying mechanism of resistance, and 3) determine the effectiveness of postemergence herbicides for controlling IMI-R populations. A previously known imazamox susceptible (SUS) shattercane population from Rooks County, KS, was used. All three putative populations exhibited a 4.1-fold to 6.0-fold resistance to imazamox compared with the SUS population. The ALS gene sequences from all IMI-R populations did not reveal any known target-site resistance mutations. A pretreatment with malathion, which inhibits cytochrome P450, followed by imazamox at various doses, reversed the resistance phenotype of the PL8 population. In a separate greenhouse study, postemergence treatments with nicosulfuron, quizalofop, clethodim, and glyphosate resulted in ≥96% injury to all IMI-R populations. The lack of known ALS target-site mutations and the reversal of resistance phenotype by malathion suggest the possibility of metabolism-based resistance to imazamox in PL8 shattercane population.