Phenoxy herbicides (2,4-D and MCPA) are widely used to manage broadleaf weeds including Palmer amaranth (Amaranthus palmeri S. Watson), one of the most troublesome weeds in U.S. cropping systems. Previously, we documented resistance to 2,4-D and MCPA in an A. palmeri population (KCTR) from Kansas. Our recent research suggested rapid metabolism of 2,4-D bestows resistance in KCTR A. palmeri; nonetheless, the mechanism of MCPA resistance in this population is still unknown. The objectives of this research were to (1) evaluate the level of resistance to MCPA in KCTR compared with two known susceptible populations of A. palmeri, MSS and KSS; (2) study the absorption and translocation of [14C]MCPA in KCTR and MSS plants: (3) investigate the metabolic profile of [14C]MCPA in KCTR and MSS and compare those with MCPA-tolerant wheat (Triticum aestivum L.) plants; and (4) assess the possible role of cytochrome P450 enzymes (P450s) in MCPA metabolism. Experiments were conducted to assess the level of resistance in KCTR. Using [14C]MCPA, the absorption, translocation, and metabolic profiles were assessed in A. palmeri. Involvement of P450s was confirmed using malathion, a known P450 inhibitor. Regression analyses indicate that KCTR population exhibits an $\sim $3-fold resistance to MCPA. No difference in absorption of [14C]MCPA was found between MSS and KCTR. However, the KCTR plants translocated less [14C]MCPA at 48 h after treatment (HAT) and metabolized MCPA more rapidly than MSS plants at 12 and 24 HAT. MCPA resistance in KCTR was reversed upon treatment with malathion, indicating the involvement of P450s in metabolism of this herbicide. This is the first report of characterization of MCPA resistance in A. palmeri.