Even though groundwater-based irrigation has increased agricultural productivity and economic activity in the United States (US), the current rate of groundwater withdrawals from major aquifers could significantly affect the sustainability of agricultural production systems in the near future. In the major agricultural regions, producers are now facing challenges to irrigate to meet full crop water needs. There is an increasing need to strategize irrigation management under various climatic and environmental conditions to optimize water use in agriculture while optimizing crop yields. This study reviews some of the major challenges facing irrigated agriculture in the US and the potential measures to ensure the sustainability of groundwater-based irrigation. Identified challenges included diminishing quantity and quality of groundwater resources, frequent droughts, low adoption rates of precision irrigation technologies, and rising energy requirements for irrigation abstractions. Irrigation efficiency improvements, shifting to high water use efficiency crops, wastewater reuse, groundwater monitoring, availing incentives, and policy changes, were identified as promising water management strategies to ensure irrigation sustainability. The success of these strategies will depend on the uptake and adoption by the producers in the affected agricultural regions.