Common lambsquarters (Chenopodium album L.) is one of the most troublesome weeds in soybean [Glycine max (L.) Merr.] and corn (Zea mays L.) fields in northeast China. In 2017, a C. album population that survived imazethapyr at the recommended field rate was collected from a soybean field in Heilongjiang Province in China. Experiments were conducted to determine the basis of resistance to imazethapyr and investigate the herbicide-resistance pattern in C. album. Dose–response tests showed that the resistant population (R) displayed high resistance to imazethapyr (20-fold) compared with the susceptible population (S). An in vitro acetolactate synthase (ALS) activity assay indicated that the ALS of the R population was resistant to imazethapyr compared with the ALS of the S population. Sequence analysis of the ALS gene revealed that the GCA was replaced by ACA at amino acid position 122, which resulted in an alanine to threonine substitution (Ala-122-Thr) in the R population. The R population displayed cross-resistance to thifensulfuron-methyl and flumetsulam but susceptibility to bispyribac-sodium, flucarbazone, glyphosate, mesotrione, and fomesafen. These results confirmed that the basis of imazethapyr resistance in C. album was conferred by the Ala-122-Thr substitution in the ALS enzyme. This is the first report of the target-site basis of ALS-inhibiting herbicide resistance in C. album.