Mitogen-activated protein kinase (MAPK) cascades are conserved and vital signaling components in the responses to various ambient stresses. Here, we report the identification of MAPKKK18, a drought resistance associated MAPK kinase kinase in Arabidopsis. The mapkkk18 knockout mutants displayed hypersensitivity to drought stress, whereas overaccumulation of MAPKKK18 in transgenic Arabidopsis plants significantly enhanced the resistance to drought. Expression pattern analysis revealed that the inducible expression of MAPKKK18 by osmotic stress was ABA and the canonical ABA signaling pathway dependent. Furthermore, MAPKKK18 mainly exerted its regulatory roles via downstream MAPKK3. These findings uncovered important roles for MAPKKK18 in drought resistance and expanded our understanding of the MAPK pathways in modulating abiotic stress responses. (C) 2017 Elsevier Inc. All rights reserved.