Increases in the yield of wheat, a major cereal crop grown in semiarid and temperate regions of the world, are often limited by drought. In this chapter, we quantitatively evaluated the effects of drought stress on the morphophysiological and biochemical characteristics, growth and biomass partitioning, and yield formation of diploid (2n), tetraploid (4n), and hexaploid (6n) wheat using a meta-analysis of published data. The study synthesized results from 303 papers published before May 2015, taking into account wheat ploidy level, rooting environment (pots or field), spring or winter type, and drought stress at different phenological stages. Drought stress reduced yields more in 2n wheat than 4n and 6n wheat due to a greater reduction in grain number and seed size; reduced aboveground biomass more in 2n and 4n than 6n wheat, but reduced root biomass more in 6n than 2n and 4n wheat; and gas exchange more in 4n wheat than 6n wheat; while major biochemical parameters increased more in 2n and 4n wheat than in 6n wheat. Across all ploidy levels, drought stress in the reproductive phase affected grain yield more than drought stress in the vegetative stage. Wheat grown in pots with limited rooting capacity had a greater reduction in yield, yield components and biomass, and greater increases in stress-induced biochemical parameters, than plants grown in the field. Drought stress reduced yields of spring wheat more than winter wheat. Domestication and selection of higher ploidy wheat have reduced the adverse effects of drought stress on yield and yield components, optimized biomass allocation toward higher seed yields, and reduced stress-related physiological and biochemical responses.