Accounting for 53% of U.S. peanuts (Arachis hypogaea L.), Georgia is the top peanut-producing state, with approximately 1.42 billion kg produced in 2023. Peanut producers often use the acetolactate synthase (ALS) imidazolinone herbicide imazapic, but reduced yellow nutsedge (Cyperus esculentus L.) control was reported in Georgia peanuts after 4 yr of continuous imazapic use. This study aimed to determine the level of resistance (LD50, I50, and GR50) and potential cross-resistance for the suspected resistant population and to identify the associated genetic mutations conferring resistance. A susceptible biotype was treated with 0, 0.0088, 0.0175, 0.035, 0.07, 0.14, 0.28, and 0.56 kg ai ha−1, and a resistant biotype was sprayed with 0, 0.07, 0.14, 0.28, 0.56, 1.13, 2.26, and 4.5 kg ai ha−1 of imazapic. To determine whether the suspected resistant biotype was cross-resistant to halosulfuron-methyl, an ALS herbicide used to control Cyperus spp., both biotypes were treated with 0, 0.0117, 0.0233, 0.0466, 0.0933, 0.187, 0.373, and 0.746 g ai ha−1 of halosulfuron-methyl. Plants were rated for injury at 7, 14, and 28 d after treatment (DAT), and aboveground biomass was harvested at 28 DAT. For imazapic, LD50 was 0.041 and 1.503 kg ai ha−1 and the GR50 was estimated to be 0.0128 and 1.853 kg ha−1 for Sus and Res biotypes, respectively, indicating 36- and 145-fold increase in resistance of the Res biotype for I50 and GR50, respectively. Both biotypes responded similarly to applications of halosulfuron-methyl, with biomass reduction at rates greater than 0.023 kg ai ha−1. Transcriptome profiles revealed a mutation in the target-site gene of the resistant biotype causing an amino acid substitution from alanine to valine at position 205 (Ala-205-Val). Growers should continue to rotate chemistries and implement integrated weed management approaches for control of C. esculentus, as the use of imazapic over consecutive years has led to resistance in C. esculentus.