Background: Adolescence and young adulthood are important developmental periods. Screening for health compromising behaviours and mental health disorders during routine primary care visits has the potential to assist clinicians to identify areas of concern and provide appropriate interventions. The objective of this systematic review is to investigate whether screening and subsequent interventions for multiple health compromising behaviours and mental health disorders in primary care settings improves the health outcomes of young people. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, literature searches were conducted in Medline, PsycINFO, Scopus and Cochrane Library databases (Prospero registration number CRD42013005828) using search terms representing four thematic concepts: primary care, young people, screening, and mental health and health compromising behaviour. To be eligible for inclusion, studies had to: include a measure of health outcome; include at least 75 % of participants aged under 25 years; use a screening tool that assessed more than one health domain; and be conducted within a primary care setting. Risk of bias was assessed using the Quality Rating Scale. Results: From 5051 articles identified, nine studies fulfilled the inclusion criteria and were reviewed: two randomised controlled trials (RCTs), one pilot RCT, two clustered RCTs, one randomised study with multiple intervention groups and no control group, one cluster RCT with two active arms, one longitudinal study and one pre-post study. Seven studies, including two RCTs and one clustered RCT, found positive changes in substance use, diet, sexual health or risky sexual behaviour, alcohol-related risky behaviour, social stress, stress management, helmet use, sleep and exercise. Of only two studies reporting on harms, one reported a negative health outcome of increased alcohol use. Conclusions: There is some evidence that the use of screening and intervention with young people for mental health disorder or health compromising behaviours in clinical settings improves health outcomes. Along with other evidence that young people value discussions of health risks with their providers, these discussions should be part of the routine primary care of young people. Further quality studies are needed to strengthen this evidence.