Climate change is increasing mean and extreme temperatures in the Southwestern United States, leading to a suite of changes affecting agricultural production. These include changes in water, soils, pathogens, weeds, and pests comprising the production environment. The aim of this synthesis is to describe the anticipated leading agricultural pressures and adaptive responses, many of which are near-term actions with longer-term consequences. In the semiarid Southwestern United States, climate change is expected to increase water scarcity. Surface water shortage is the leading reason for recent diminished crop yields in the Southwest. Drought and lack of water represent the leading regional weather-related cause of crop loss from 1989 to 2017. Thus, water scarcity has been and will continue to be a critical factor leading to regional crop vulnerability. Soils, pathogens, weeds, and insects are components of the agricultural production environment and are directly influenced by near-term weather and long-term climate conditions. Field crops, vegetable crops, and perennial crops have unique production requirements and diverse management options, many already used in farm management, to cope with production environment changes to build climate resilience. Farmers and ranchers continuously respond to changing conditions on a near-term basis. Long-term planning and novel adaptation measures implemented may now build nimble and responsive systems and communities able to cope with future conditions. While decision-support tools and resources are providing increasingly sophisticated approaches to cope with production in the 21st century, we strive to keep pace with the cascading barrage of inter-connected agricultural challenges.