Agriculture is an important industry in the Yangtze River Delta. Agricultural non-point source pollution has brought severe challenges to water security, food security, and ecological safety in the Yangtze River Delta; therefore, it is urgent to synergistically manage agricultural non-point source pollution through co-governance of water resource protection, water pollution control, and aquatic ecosystem restoration, thereby safeguarding the high-quality and integrated development of the Yangtze River Delta. This study systematically analyzes the challenges faced in the management of agricultural non-point source pollution in the region: large agricultural water consumption and low recycling rate; complex composition of agricultural non-point source pollution and variable production and transportation process; mutual interaction of regional planting and breeding with superimposed pollution emissions; lack of coordination between water quality improvement, water quantity, and aquatic ecosystem; unclear responsibility of non-point source pollution governance entities; and difficulties in long-term operation and maintenance of engineering projects. The study proposes the following suggestions for the system construction aimed at synergistic governance of agricultural non-point source pollution in the Yangtze River Delta: (1) constructing a regional circular wetland system for farmland to facilitate the recycling of water, fertilizer, and pesticides; (2) leveraging irrigation and drainage systems to realize stepwise interception and purification of farmland pollutants; (3) coordinating the integrated use of water and fertilizer for planting and breeding to achieve near-zero emission of non-point source pollutants; (4) integrating the governance of water resource protection, water pollution control, and aquatic ecosystem restoration to establish technical standards and management paradigms; and (5) establishing a platform for co-governance to enhance the comprehensive control system for water resources, environment, and ecology in the Yangtze River Delta.