In previous studies, we imaged chemical gradients of small molecules along the developmental axis of maize roots and revealed citric acid cycle (CAC) metabolites to have new roles in root development. Itaconate, a secondary metabolite derived from the CAC metabolite cis- aconitate, shows a developmentally enriched metabolomic profile in maize roots. Itaconate functions in mammalian immune responses, reactive oxygen species (ROS) scavenging, and post translation modifications of proteins. However, its role in plants remains largely uncharacterized. To understand itaconate’s role in maize and Arabidopsis, plants were exogenously treated with itaconate. We show itaconate hampers the development of Arabidopsis, increases shoot growth of maize, and we identify itaconate’s relationship to multiple processes: reprogramming metabolism, nutrient stress, environmental stress, phytohormone induction, and protein biosynthesis. Furthermore, itaconate induces variability producing resistant seedlings more tolerant to salt and drought stress compared to control-treated plants. To identify the itaconate mechanism, Drug Affinity Response Target Stability (DARTS) assay was performed to discover itaconate-proteins interactors. We find numerous proteins involved in the ABA pathway including the major protein class Sucrose Non-Fermenting Related protein Kinase (SNRK). Our results demonstrate that itaconate is an endogenous molecule with potent effects on development and stress response. We hypothesize itaconate affects these processes through direct post-translational modifications, including an ABA-dependent activation of SNRKs and regulation of proteins. We anticipate itaconate may be an essential tool to produce stress tolerant food crops and predict the findings of this study will be the basis of a new field: understanding and engineering itaconate signaling in plants.