Sustainable Development Goal 6 (SDG-6) addresses poor water quality, inadequate sanitation, and improper hygiene, all of which negatively impact health and disproportionately impact Indigenous Peoples’ health. Understanding and responding to local contexts is critical to effectively improve water, sanitation, and hygiene (WASH); however, in-depth understanding of local knowledge, practices, and perceptions are often overlooked. As such, this study described the knowledge, practices, and perceptions of WASH held by residents of two Indigenous Shawi communities in the Peruvian Amazon. Quantitative data were collected via a cross-sectional survey and analyzed using descriptive statistics. Qualitative data were collected via interviews, PhotoVoice, focus group discussions, and participatory transect walks, and analyzed using a constant comparative approach to thematic analysis. Emergent themes included characterizing water sources, collection methods, and consumption patterns; knowledge, perceptions, and practices related to WASH; and knowledge and perceptions of health issues related to WASH. This study provides insight into the ongoing challenges related to WASH in Indigenous communities in the Peruvian Amazon and highlights the need to prioritize interventions that will advance WASH-related SDGs.