Theoretical models and empirical research point to negatively biased attention as a maintaining factor in depression. Although preliminary studies suggest experimentally modifying attentional biases (i.e., attentional bias modification; ABM) reduces depression symptoms and depression risk, relatively few rigorous studies with clinical samples have been completed. This clinical trial examines the impact of ABM on a sample of adults (N = 123) with elevated depression severity who also exhibit at least modest levels of negatively biased attention prior to treatment. Participants will be randomly assigned to either active ABM, placebo ABM, or an assessment-only control condition. Individuals assigned to ABM will complete 5 trainings per week (2 in-clinic, 3 brief trainings at-home) during a four-week period. Throughout this four-week period, participants will complete weekly assessments of symptom severity and putative treatment mediators measured across different levels of analysis (e.g., eye tracking, behavioral measures, and functional Magnetic Resonance Imaging). This article details the rationale and design of the clinical trial, including methodological issues that required more extensive consideration. Our findings may not only point to an easily-accessible, efficacious treatment for depression but may also provide a meaningful test of whether a theoretically important construct, negatively biased attention, maintains depression.