Lack of sufficient water is a major limiting factor to crop production worldwide, and the development of drought-tolerant germplasm is needed to improve crop productivity. The phytohormone ethylene modulates plant growth and development as well as plant response to abiotic stress. Recent research has shown that modifying ethylene biosynthesis and signaling can enhance plant drought tolerance. Here, we report novel negative regulators of ethylene signal transduction in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). These regulators are encoded by the ARGOS gene family. In Arabidopsis, overexpression of maize ARGOS1 (ZmARGOS1), ZmARGOS8, Arabidopsis ARGOS homolog ORGAN SIZE RELATED1 (AtOSR1), and AtOSR2 reduced plant sensitivity to ethylene, leading to enhanced drought tolerance. RNA profiling and genetic analysis suggested that the ZmARGOS1 transgene acts between an ethylene receptor and CONSTITUTIVE TRIPLE RESPONSE1 in the ethylene signaling pathway, affecting ethylene perception or the early stages of ethylene signaling. Overexpressed ZmARGOS1 is localized to the endoplasmic reticulum and Golgi membrane, where the ethylene receptors and the ethylene signaling protein ETHYLENE-INSENSITIVE2 and REVERSION-TO-ETHYLENE SENSITIVITY1 reside. In transgenic maize plants, overexpression of ARGOS genes also reduces ethylene sensitivity. Moreover, field testing showed that UBIQUITIN1:ZmARGOS8 maize events had a greater grain yield than nontransgenic controls under both drought stress and well-watered conditions.There is an increasing demand for food and feed due to global population growth, urbanization, and rapid middle-class emergence. Lack of water limits crop yields worldwide; Bot et al. (2000) estimated that 45% of agricultural lands are subject to continuous or frequent drought conditions. Drought-tolerant varieties can reduce the impact of drought on crop productivity. The phytohormone ethylene regulates many aspects of plant growth and development, from seed germination, leaf expansion, and floral transition to organ senescence, fruit ripening, and the response to abiotic stresses, such as drought, high temperature, freezing, shading, and nutrient deficiency. Ethylene is one of the most widely used hormones in agriculture to increase yield and reduce production costs. For example, ethylene can reduce lodging in wheat (Triticum aestivum) and barley (Hordeum vulgare) by shortening the stem, therefore improving grain yield and quality. Studies have shown that inhibitors of ethylene biosynthesis and perception can mitigate yield loss by enhancing plant tolerance to abiotic stresses, such as drought, heat, and a combination of both (Hays et al., 2007;Kawakami et al., 2010Kawakami et al., , 2013Huberman et al., 2014). This study explores the potential to improve crop performance by modifying ethylene sensitivity.At the molecular level, ethylene responses in Arabidopsis (Arabidopsis thaliana) are initiated by the binding of ethylene to a family of endoplasmic reticulum (ER)-and Golgi membrane-localized receptors...