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Importance: Despite the magnitude of alcohol use problems globally, treatment uptake remains low. Telephone-delivered interventions have potential to overcome many structural and individual barriers to help seeking, yet their effectiveness as a stand-alone treatment for problem alcohol use has not been established., Objective: To examine the effectiveness of the Ready2Change telephone-delivered intervention in reducing alcohol problem severity up to 3 months among a general population sample., Design, Setting, and Participants: This double-blind, randomized clinical trial recruited participants with an Alcohol Use Disorders Identification Test (AUDIT) score of greater than 6 (for female participants) and 7 (for male participants) from across Australia during the period of May 25, 2018, to October 2, 2019. Telephone assessments occurred at baseline and 3 months after baseline (84.9% retention). Data collection was finalized September 2020., Interventions: The telephone-based cognitive and behavioral intervention comprised 4 to 6 telephone sessions with a psychologist. The active control condition comprised four 5-minute telephone check-ins from a researcher and alcohol and stress management pamphlets., Main Outcomes and Measures: The primary outcome was change in alcohol problem severity, measured with the AUDIT total score. Drinking patterns were measured with the Timeline Followback (TLFB) instrument., Results: This study included a total of 344 participants (mean [SD] age, 39.9 [11.4] years; range, 18-73 years; 177 male participants [51.5%]); 173 participants (50.3%) composed the intervention group, and 171 participants (49.7%) composed the active control group. Less than one-third of participants (101 [29.4%]) had previously sought alcohol treatment, despite a high mean (SD) baseline AUDIT score of 21.5 (6.3) and 218 (63.4%) scoring in the probable dependence range. For the primary intention-to-treat analyses, there was a significant decrease in AUDIT total score from baseline to 3 months in both groups (intervention group decrease, 8.22; 95% CI, 7.11-9.32; P < .001; control group decrease, 7.13; 95% CI, 6.10-8.17; P < .001), but change over time was not different between groups (difference, 1.08; 95% CI, -0.43 to 2.59; P = .16). In secondary analyses, the intervention group showed a significantly greater reduction in the AUDIT hazardous use domain relative to the control group at 3 months (difference, 0.58; 95% CI, 0.02-1.14; P = .04). A greater reduction in AUDIT total score was observed for the intervention group relative to the control group when adjusting for exposure to 2 or more sessions (difference, 3.40; 95% CI, 0.36-6.44; P = .03) but not 1 or more sessions (per-protocol analysis)., Conclusions and Relevance: Based on the primary outcome, AUDIT total score, this randomized clinical trial did not find superior effectiveness of this telephone-based cognitive and behavioral intervention compared with active control. However, the intervention was effective in reducing hazardous alcohol use and reduced alcohol problem severity when 2 or more sessions were delivered. Trial outcomes demonstrate the potential benefits of this highly scalable and accessible model of alcohol treatment., Trial Registration: ANZCTR Identifier: ACTRN12618000828224.