Juvenile justice system involvement is associated with increased risk for many mental health concerns including substance use problems. Juvenile detention centers offer a primary point of contact by which youth may access programs that enhance their motivation to make positive changes. Yet, few studies have tested whether the clinical approaches that are helpful in community settings or long-term juvenile justice settings are also helpful in short-term juvenile detention facilities. Free Talk (FT) is a 6-session program that has been shown to reduce substance use among youth charged with a first-time drug offense in a youth court setting. The current study is the first evaluation of FT’s implementation in a detention center. To inform future implementations, we aimed to 1) assess whether detained youth participating in the intervention experienced the motivational changes that were expected based on studies of non-detained youth and 2) test whether depressive symptoms and substance use problems moderated the benefit of FT. Detained adolescents (N = 49; 83.7% male; M age = 15.31; 83.7% African-American, 12.2% White, 4.7% Hispanic/Latinx) participated in FT. A pre-post design suggested that, on average, youth in the sample experienced decreases in motivation to change substance use; however, youth with higher levels of substance use problems exhibited increases in motivation after participating in FT. Results emphasize the need to specifically target clinical services to those most likely to benefit from them and to avoid clinical situations that may result in iatrogenic effects. We discuss implementation challenges and recommend solutions to enhance mental health care in short-term detention centers.