Agriculture is an important cause of multiple pollutants in water. With population growth and increasing food demand, more nutrients, plastics, pesticides, pathogens and antibiotics are expected to enter water systems in the 21st century. As a result, water science has been shifting from single-pollutant to multi-pollutant perspectives for large-scale water quality assessments. This perspective paper summarizes and discusses four main highlights related to water pollution and agriculture from the multi-pollutant perspective. These highlights reveal the spatial and temporal distribution and main sources of multiple pollutants in waters. Based on the highlights, a scientific agenda is proposed to prioritize solutions for sustainable agriculture (UN Sustainable Development Goal 2) and clean water (UN Sustainable Development Goals 6 and 14). This agenda points out that when formulating solutions for water pollution, it is essential to take into account multiple pollutants and their interactions beyond biogeochemistry.