After two decades of availability of grain yield-mapping technology, long-term trends in field-scale profitability for precision agriculture (PA) systems and conservation practices can now be assessed. Field-scale profitability of a conventional or ‘business-as-usual’ system with an annual corn (Zea mays L.)-soybean (Glycine max [L.]) rotation and annual tillage was assessed for 11 years on a 36-ha field in central Missouri during 1993 to 2003. Following this, a ‘precision agriculture system’ (PAS) with conservation practices was implemented for the next 11 years to address production, profit, and environmental concerns. The PAS was dynamic and included no-till, cover crops, growing winter wheat (Triticum aestivum L.) instead of corn in a section of the field where corn was often not profitable, site-specific N for wheat and corn using canopy reflectance sensing, variable-rate or zonal P, K and lime using intensively grid-sampled data, and targeting of herbicides based on weed pressure. Differences in yield and yield variability between the two systems were recently evaluated, but profitability comparisons have not been made. Results indicated that PAS maintained profits in the majority (97%) of the field without subsidies for cover crops or payments for enhanced environmental protection. Profit or net returns were only lower with PAS in the drainage channel where no-till sometimes hindered soybean stands and wet soils caused wheat disease. Although profit gains were not realized after 11 years of PA and conservation practices, results indicate this type of system can maintain profits. Furthermore, this information should help growers gain confidence that PA and conservation practices will be successful.