During the 20th century, US agriculture underwent vast transformations. The number of farmers has decreased, more farmers are relying on off-farm income, agriculture's proportion of the US GDP has declined, and a minority of non-metro counties in the US are farming dependent. Agriculture's evolution will continue and we have identified key trends and future challenges to effectively manage our changing agricultural system. Eight current trends in US agriculture were identified. These included: (1) increased land degradation; (2) competing land uses; (3) focus on single ecosystem service; (4) increase in farm size; (5) movement toward commercialization; (6) genetic engineering; (7) global markets; and (8) changing social structure. Future trends likely to affect agriculture include: (1) diminishing and increasingly volatile farm incomes; (2) reduced government involvement in food regulation; (3) continued transition from farming to agribusiness; (4) land-use will become a major issue; (5) increasing animal protein consumption in the US; (6) increased public input on livestock production practices; (7) increasing urbanization of historically rural US counties; (8) increased public concern over food safety; (9) increased medicinal production from agriculture; (10) new tastes, markets and opportunities will emerge. We further postulated that future challenges facing US agriculture might include: (1) competitive pressures; (2) sustainable development; (3) resource conservation; and (4) research and development. Integrated agricultural systems may be flexible enough to address these challenges. However, robust principles will be needed to design adaptable integrated agricultural systems. We present a nonexclusive list of preliminary principles under the four general categories of (1) economics and economic policies; (2) environmental; (3) social and political; and (4) technological.