Abstract Phenotypic plasticity is the property of a given genotype to produce multiple phenotypes in response to changing environmental conditions. Understanding the genetic basis of phenotypic plasticity and establishing a predictive model is highly relevant for future agriculture under changing climate. Here, we investigated the genetic basis of leaf width plasticity in a tobacco MAGIC population across four different environments. Environmental changes not only resulted in differences in leaf width mean but also in leaf width plasticity. A total of 45 QTL were identified, including 14 QTL for leaf width mean and 43 for leaf width plasticity, with 12 overlap. Changes in the environment affected the magnitude of several QTL, thereby influencing phenotypic plasticity. We identified a QTL, qLW14, associated with leaf width plasticity and leaf width mean at Zhucheng, but had no significant impact at Guiyang, indicating that changes in the environment contributed to variations in leaf width plasticity. By integrating genetic diversity, environmental variation, and their interactions into a unified model, we were able to build a model for cross-environment predictions, and improved prediction accuracy by 7.2%. Overall, this study reveals complex genetic basis involving multiple alleles, and genotype interactions underlying variations of leaf width mean and plasticity. These findings contribute to assessing the role of plasticity in responding to climate or other environmental changes.