We describe an effort to develop a consensus-based research agenda for mental health and psychosocial support (MHPSS) interventions in humanitarian settings for 2021–30. By engaging a broad group of stakeholders, we generated research questions through a qualitative study (in Indonesia, Lebanon, and Uganda; n=101), consultations led by humanitarian agencies (n=259), and an expert panel (n=227; 51% female participants and 49% male participants; 84% of participants based in low-income and middle-income countries). The expert panel selected and rated a final list of 20 research questions. After rating, the MHPSS research agenda favoured applied research questions (eg, regarding workforce strengthening and monitoring and evaluation practices). Compared with research priorities for the previous decade, there is a shift towards systems-oriented implementation research (eg, multisectoral integration and ensuring sustainability) rather than efficacy research. Answering these research questions selected and rated by the expert panel will require improved partnerships between researchers, practitioners, policy makers, and communities affected by humanitarian crises, and improved equity in funding for MHPSS research in low-income and middle-income countries.