The Yamuna River, a vital water source in India, poses a profound challenge concerning water purity across its entire stretch. The comprehensive review aims to thoroughly examine the river's water quality, shedding light on the sources of pollution and their consequences for both ecological systems and public health. The primary objective of this review is to examine the published research papers concerning the Yamuna River water quality stretching from Yamunotri to Prayagraj and its resulting impact on human health. This paper also comprises a wide range of pollutants mainly caused by human activity; during the strange period of COVID-19 lockdown, when all industries were closed, resulting in changes in water quality, signifies the destructive effects of human activity on the river. Studies uncover that the most contaminated areas are Nizamuddin of Delhi region and D/S of Agra in Uttar Pradesh, which includes the foremost level of faecal coliforms to be around 210000–11000000 and 450–6100000, respectively. The total coliforms were found to be between 700000–28000000 and 2200–32000000, respectively. Biochemical oxygen demands, industrial discharge, urban waste and agriculture are identified as the most responsible factors for this contamination. After the COVID-19 lockdown, all industries were open, and now, the conditions are the same as before COVID-19. The primary insight to be assembled is that the ecological balance of the Yamuna River and public health depend on the immediate requirement for effective wastewater treatment solutions. Besides offering valuable data by compiling findings from multiple studies, this review underscores the importance of implementing stringent regulations on industrial emissions, upgrading sewage treatment plants, and promoting eco-friendly farming methods to tackle pollution in the Yamuna River and also manage the rural and urban areas of the sewage pipeline plan. It stresses the importance of safeguarding the Yamuna River ecosystem's inherent socioeconomic benefits while alleviating the environmental harm caused by pervasive pollution. Essentially, the study calls for prompt and comprehensive measures to ensure the sustainable health of this crucial water resource in India.