This randomized controlled trial tested the efficacy of a multi-session, evidence-based, lay counselor-delivered transdiagnostic therapy, the Common Elements Treatment Approach (CETA), in reducing unhealthy alcohol use and comorbidities among persons living with HIV (PLWH) in Zambia. Adult PLWH with (a) unhealthy alcohol use plus mental health or substance use comorbidities, or (b) severe unhealthy alcohol use were randomized to receive a single-session alcohol brief intervention (BI) alone or BI plus referral to CETA. Outcomes were measured at baseline and a 6-month follow-up and included Alcohol Use Disorders Identification Test (AUDIT) score (primary), depression and trauma symptoms, and other substance use (secondary). We enrolled 160 participants; 78 were randomized to BI alone and 82 to BI plus CETA. Due to COVID-19, the trial ended early before 36 participants completed. Statistically and clinically significant reductions in mean AUDIT score from baseline to 6-month follow-up were observed in both groups, however, participants assigned to BI plus CETA had significantly greater reductions compared to BI alone (− 3.2, 95% CI − 6.2 to − 0.1; Cohen's d: 0.48). The CETA effect size for AUDIT score increased in line with increasing mental health/substance use comorbidity (0 comorbidities d = 0.25; 1-2 comorbidities d = 0.36; 3+ comorbidities d = 1.6). Significant CETA treatment effects were observed for depression, trauma, and several other substances. BI plus referral to CETA was feasible and superior to BI alone for unhealthy alcohol use among adults with HIV, particularly among those with comorbidities. Findings support future effectiveness testing of CETA for HIV outcomes among PLWH with unhealthy alcohol use. Clinical Trials Number: NCT03966885