Arsenic, the 20th most common element in Earth’s crust and historically regarded as the King of Poisons, occurs naturally in two oxidation states, Arsenate (V) and Arsenite (III), and is prevalent worldwide through natural and anthropogenic means. The cations of the metalloid exhibit unique chemical behaviour in water and are found to be components of approximately 245 natural minerals, making its occurrence in drinking water a compelling challenge, especially in groundwater. This comprehensive review collates information regarding the prevalence of arsenic contamination in water worldwide and its impact on human health, its chemical behaviour, methods for detection and quantification, and treatment strategies. A comprehensive search was conducted, and the selection of eligible studies was carried out using the PRISMA (the preferred reporting items for systematic reviews and meta-analyses) guidelines. Essential characteristics of eligible research studies were extracted based on geographical areas, origins, concentration levels and the magnitude of populations vulnerable to arsenic contamination in groundwater sources. Arsenic contamination of water affects over 100 countries including Canada, the United States, Pakistan, China, India, Brazil and Bangladesh, where hydrogeological conditions favour prevalence and groundwater is the primary water source for food preparation, irrigation of food crops and drinking water. This leads to human exposure through absorption, ingestion and inhalation, causing numerous health disorders affecting nearly all systems within the human body, with acute and chronic toxicity including cancers. The presence of arsenic in water poses a considerable challenge to humanity, prompting scientists to devise diverse mitigation approaches categorized as (a) oxidation processes, (b) precipitation methods, (c) membrane technologies, (d) adsorption and ion exchange methods, and (e) social interventions. This comprehensive review is expected to be a valuable source for professionals in the water industry, public management, and policymaking, aiding their ongoing and future research and development efforts.