Moisture stress limits the yield and productivity of wheat, a staple food for 35% of the world’s population. The reproductive stage is the most vulnerable to moisture deficit, and genetic variation for tolerance to stress has been identified in the wheat gene pool. Introducing this complex variation into new, pure-line cultivars is difficult and time consuming. However, varietal mixtures can be an effective alternative to traditional gene pyramiding. Varietal mixtures lessen the impacts of abiotic and biotic stresses in two ways. First, they buffer yield through more efficient resource use, including soil moisture, particularly evident when mixtures comprise complementary physiological traits that influence water-use efficiency. Second, they improve resistance to root diseases and pests that limit root growth and subsequent access to, and absorption of, water from deeper in the soil profile. This review evaluates the concept of varietal mixtures and assesses their impact on crop productivity and environmental buffering. The potential of physiological and root disease resistance trait mixtures to stabilise yield is also explored. Avenues for developing compatible mixtures based on physiological traits that increase yield in water-limited environments are evaluated.