Background: Infection prevention and control (IPC) is recognised as essential to addressing the emergence and spread of antimicrobial resistance (AMR) in human health, food production and the environment. How best to address this through a One Health perspective remains a challenge. This systematic review addresses this gap by identifying and synthesising evidence from interventions designed to improve water, hygiene, sanitation (WASH), and biosecurity in animal agriculture and in people that live and/or work with animals. This review aimed to capture evidence of effects of all types of intervention and across different settings. Methods: We conducted a systematic search for studies that reported on WASH and biosecurity interventions with the potential to reduce the burden of infections and reliance on antibiotics in animal production for populations living with animals and/or involved in agriculture/aquaculture with a primary focus on LMICs. We searched the following databases: Web of Science, PubMed, OVID, ProQuest, Epistemonikos, Trip, AgEcon, and Cochrane Library. For articles in Spanish, we searched Scielo, BIREME, E-Revistas, Redalyc, Lilacs, AfricaPortal, IMSEAR and WPRIM. A hand search of literature was also conducted in relevant sources, and Google Scholar and Open Grey were used for grey literature. The main outcomes of interest were: (i) reduction of infections/cases, (ii) reduction of bacterial load, and (iii) reduction of antimicrobial use and AMR. We extracted data from selected studies, performed a narrative synthesis, and developed a framework. PROSPERO Registration: The protocol for the systematic review was registered at PROSPERO, registration number CRD42020162345. Findings: A total of 104 studies were included in this systematic review. The majority of studies (64/104) (61.5%) were conducted in HICs, especially in Europe and the USA. Only 13 (12.5%) studies took place in LMICs. The majority of studies (77) were animal based, followed by 12 targeting both animals and the environment, nine focused exclusively on the environment, and only one study was exclusively about humans. Most studies were conducted in poultry (36) and pigs (27), and assessed impacts on multiple types of bacteria (commonly Salmonella spp. and Campylobacter spp.). Eighty-seven (87) studies assessed impact on IPC, 3 on AMU, and 14 on AMR. The interventions were classified as follows: 57 applied biological or chemical products to eliminate pathogens; 26 modified infrastructure and apparatus; 15 were educational/behavioural and one was a structural intervention. Around 52.8% (55/104) studies included WASH interventions focused on water quality (20), water quantity (2), hygiene (30), and sanitation (3). Likewise, 47.1% (49/104) included biosecurity interventions focused on bio-management (34), bio-containment (10), and bio-exclusion (5). Positive impacts were reported for 64 (61.5%) interventions, on infection burden (54/87), antibiotic use (3/3) or AMR (7/14). The majority were non-randomised studies (55), although a quarter were randomised controlled trials (26). A total of 27 studies were classified as having low risk of bias, 21 moderate and 56 high risk of bias. Interpretation: This review identifies a number of effective interventions to reduce the burden of infections, antimicrobial resistance and antibiotic use in animal agricultural settings. Interventions which undertook bio-management and bio-containment measures appeared to have positive effects most often. These measures attempted to create and maintain a conducive environment for animal raising in terms of physical infrastructure and protocols. The few studies reporting sanitation measures - which were similar to bio-containment interventions - all reported positive effects. By contrast, efforts to impact water quantity, water quality, and hygiene had more mixed effects on the outcomes assessed. Bio-exclusion interventions had mostly negative effects. Risk of bias was high or moderate in many studies, however, and publication bias should also be considered. The paucity of studies evaluating structural interventions needs to be addressed. There are opportunities to learn from biosecurity Interventions for WASH and we propose the 'A' In WASH represents both 'Animals' and 'Air' in recognition of pathways of infection that can be addressed to also impact AMR.