Utility-scale solar energy (USSE) is rapidly expanding and expected to compose the largest source of renewable-generated electricity in the United States and globally over the coming decades. Lands in the hot Desert Southwest (Chihuahuan, Mojave, Sonoran, and San Joaquin Deserts) are increasingly selected for USSE development because of their high solar irradiance. The Desert Southwest supports high biodiversity and provides many ecosystem services but is vulnerable to USSE disturbance and simultaneous stress from aridification and other growing land-use pressures. In this review, a framework is presented for predicting the effects of USSE development on plants and wildlife by linking disturbance types associated with USSE construction and operation to the traits and response strategies of species and guilds. Case studies from representative Desert Southwest species and guilds of conservation concern are used to: review known effects of USSE, predict unknown effects with the trait-based framework, and discuss mitigation strategies. This framework predicts that species with trait plasticity and broad ecological niches will be capable of exploiting USSE development, while species with specific habitat requirements and narrow niches will be more vulnerable. Opportunities for mitigation during development and operation that may lessen these effects are identified. This work is intended to inform USSE management decision-making and long-term planning, as well as encourage new research to test predicted effects and responses.