BackgroundTrauma is an experience (physical or emotional) that is life-threatening, harmful, or out of the ordinary and has lasting effects on mental health and wellbeing. Much of the information about trauma within homeless populations focuses on events in childhood. Using coproduction principles, we aimed to synthesise qualitative evidence exploring the impact of trauma during adulthood homelessness on mental health, including substance use. MethodsIn this qualitative systematic review, we searched ASSIA, CINAHL, Cochrane, EMBASE, MEDLINE, Proquest theses and dissertations, PsychInfo, Scopus, and Web of Science for studies published from inception until Sept 6, 2022, alongside grey literature from relevant websites. Search terms were developed based on the PICO framework. No language, date, or geographical limits were applied. Any qualitative research reporting experiences of trauma and its impact on mental health during homelessness in adults was eligible. We extracted relevant data (eg, methodology, sample characteristics, homelessness, and findings). People with lived experience of homelessness were provided with bespoke training by the lead researcher. They contributed to refining the review aims, screening, coding, and theme development. Quality was assessed using the CASP Qualitative Studies Checklist. FindingsWe included 26 qualitative papers, including 876 adults experiencing homelessness between ages 18 and 70 years (448 [51%] women and 428 [49%] men). All papers focused on urban settings. Eight papers were from the USA, five from Canada, four from the UK and Australia, three from Brazil, and one from Ethiopia and Iran. A framework synthesis of these 26 papers identified three preliminary themes. People experiencing homelessness make sense of trauma in three ways: internalised understanding, relationality to others, and with a survival lens. Coping strategies for managing feelings of fear, anxiety, and depression included substance use, self-rationalisation, and strategies to feel safe. Finally, when people experienced repeated trauma, they became either dissociated, and accepted their situation, or resilient, wishing to change their circumstances. InterpretationFurther evidence is needed in rural or coastal regions, where people experiencing homelessness may face greater isolation. Trauma rarely takes place in isolation, and often previous experiences of trauma shape how people experiencing homelessness make sense of trauma and cope with it. Support to address coping with the effects of trauma should focus on ensuring people do not become desensitised and prevent deterioration of mental health and substance use. The strength of this review is its coproduction with people with lived experience. Single person data extraction with secondary checks was a limitation. FundingNational Institute for Health and Care Research (NIHR) School for Primary Care Research as part of the Three NIHR Research Schools Mental Health Programme.