BackgroundAgriculture provides a vital contribution to Wales through supporting livelihoods and communities and shaping the landscape. Experiencing periods of uncertainty can affect not only the farming business and financial circumstances, but also farmers’ mental health and wellbeing, with longer-term effects on livelihoods, farming culture, and sense of identity. We aimed to develop an evidence-informed framework to support the mental health and wellbeing and resilience of farmers. MethodsWe searched MEDLINE, Embase, PsycINFO, NICE, and Cochrane databases for keywords associated with farmers, mental health, wellbeing, resilience, support, and suicide. Studies of any design, published in English between Jan 1, 2005 and March 8, 2019 were eligible for inclusion. This evidence was further supported by stakeholder engagement through two world café-style workshops (n=19), face-to-face consultation with farmers at two agricultural events (n=19), and semi-structured telephone interviews with stakeholders (n=7). Challenges, existing support, and the relevance of the evidence reviewed were discussed. Engagement was recorded through researcher's field notes and analysed thematically. FindingsA total of 843 records were identified (after duplicate removal), screened by title, and abstract, with 130 full-text records examined. 14 reports were included in the final review. We identified three key, evidence-based international programmes with transferability to Wales, which were centred on health promotion, mental health literacy, and cross-agency partnership development. The qualitative engagement uncovered 11 distinct challenges facing farmers, with business viability, stress from workload (financial, administrative, and physical), and stigma being barriers to seeking advice and support to address the underlying causes of stress. InterpretationThe evidence from the review and engagement are brought together to create an action framework for supporting farmers that is particularly relevant during times of increased uncertainty. Support should be two-fold: to prevent the effects of uncertainty to farming business; and to protect farmers’ mental health and wellbeing with early prevention, awareness-raising, and normalisation of mental health in agriculture. Interventions could build upon existing initiatives, using an outreach-based model and peer-to-peer delivery, widening access to farming family members and including Welsh language provision. FundingWelsh Government European Transition Fund.