Background: Preventive interventions to delay substance use disorder (SUD) are ideally delivered during early adolescence, a critical period for exposure to substance use (SU) risk factors. Young teens (aged 12-14 years) engaging in occasional use of alcohol, cannabis, or tobacco use, or with a family history of SUD, are at increased risk for SUD. Although behavioral-ecological family therapy is effective for prevention, many families face access barriers. Single-session interventions (SSIs) may offer an accessible, low-intensity alternative. Objective: This open pilot trial aimed to evaluate the acceptability, #feasibility, and potential usefulness of a family-based SSI targeting improvements in family practices that prevent SUD. Methods: Participants were 9 young teens engaging in occasional SU or with a family history of SUD and their parent. The SSI involved a virtual 2-hour family consultation with a trained family coach. Acceptability was measured via Program Feedback Scale, #feasibility via SSI completion rate, and potential usefulness via pre-post changes in parenting self-efficacy. Results: The SSI was acceptable to parents and teens (mean Program Feedback Scale scores ≥3) and feasible (8/9, 88.89% of parent-teen dyads completed the SSI). Among the 8 completing dyads, most participants (13/16, 81.25%) selected Communication and Problem Solving as their primary target for change. Parents reported increases in parenting self-efficacy from pre- to post-SSI. Conclusions: Findings support the SSI’s acceptability and #feasibility for young teens at high risk for SUD. A randomized clinical trial is needed to confirm the SSI’s acceptability, #feasibility, and efficacy, as well as to address potential for delivery by a lay workforce. Trial Registration: ClinicalTrials.gov NCT06538922; https://clinicaltrials.gov/study/NCT06538922