Water, sanitation, and hygiene (WASH) interventions are key to reducing the burden of disease associated with outbreaks, and are commonly implemented in emergency response. However, there is a lack of summarized evidence on the efficacy and effectiveness of these interventions. We conducted a systematic review of published and grey literature by developing theory of change models, developing inclusion criteria, conducting the search, selecting evaluations for inclusion, assessing the quality of the evidence, and analysing the included evaluations. Overall, 15,026 documents were identified and 51 evaluations from 47 studies met inclusion criteria. Interventions from 19 countries were included, primarily in response to cholera (86 per cent). Most included evaluations (70 per cent) were at high risk of bias and nearly half were from grey literature (49 per cent). We found that WASH interventions consistently reduced both the risk of disease and the risk of transmission in outbreak contexts; however, programme design and beneficiary preferences were important considerations to ensure WASH intervention effectiveness. Critical programme design characteristics included simple interventions that were appropriately timed, community-driven, and had linkages between relief and development. Beneficiary preferences, barriers, and facilitators to WASH interventions in outbreak response were taste and smell of water treatment, communication methods, inaccurate perception of efficacy, and trust/fear. Research on commonly implemented but severely under-researched WASH interventions is recommended. It is also recommended that responders implement interventions that are: efficacious, simple, well-timed, community-driven, link relief and development, and address barriers and facilitators to use with communities.