Conventional cultivation of claypan soils leads to soil and water quality degradation because of high runoff and associated soil erosion. The Goodwater Creek Experimental Watershed, which is part of the USDA Agricultural Research Service Benchmark Conservation Effects Assessment Project, Watershed Assessment Studies, was established to address these issues. Plot studies have highlighted trade-offs between erosion control and herbicide or nutrient runoff. There is a need for long-term field-scale evaluation of combined practices that reduce sediment, nutrient, and herbicide losses by runoff. A 36 ha field located in Missouri was under a conventional corn (<i>Zea mays</i> L.)–soybean (<i>Glycine max</i> L.) system from 1993 to 2003 with fertilizer application and tillage prior to planting in the spring. A precision agriculture system defined by two main management zones was implemented from 2004 to 2014: wheat (<i>Triticum aestivum</i> L.) and soybean in 60% of the field, and corn and soybean in the remaining 40%. The system included no-till, cover crops, atrazine split-applications based on weed pressure, variable rates of nitrogen (N), and variable rates of fall-applied phosphorus (P). The objective of this study was to compare runoff water quality from the two management systems, based on flow and load duration curves, cumulative distribution functions, and conclusions from replicated plot studies. The precision agriculture system did not affect annual runoff, but it did increase the frequency of low flows. Sediment losses were reduced by 87% as a result of no-till and cover crops. Atrazine and P losses were lower than expected, despite the lack of incorporation into the soil. Atrazine losses were possibly lower because of the wheat area acting as a buffer, greater atrazine adsorption and retention in the field, and faster decay. Dissolved P losses as a fraction of applied remained the same, likely because of greater adsorption and lower runoff risk when applying P. Finally, nitrate-N (NO<sub>3</sub>-N) losses decreased and resulted in an overall decrease of N losses despite a slight increase of ammonium-N (NH<sub>4</sub>-N) losses. Explanations included a greater soil water content, a different timing of N applications, and N uptake by cover crops. Building on these successes, an aspirational management system is proposed to further improve on the performance and practicality of the precision agriculture system.