Ecological intensification of agriculture is a proposed strategy to enhance the production of food while expanding ecosystem services and reducing inputs. Perennial plants that are directly harvested for human food are a novel means of ecological intensification, by potentially providing unprecedented levels of ecological services, such as increased soil carbon and reduced nutrient leaching. However, existing herbaceous perennial plants produce low yields of harvestable seed. Therefore, we initiated a domestication program to improve the grain yield of the perennial intermediate wheatgrass (Thinopyrum intermedium [Host] Barkworth & D.R. Dewey). The breeding program has adapted to changing resources and to results from previous generations, with methods becoming more elaborate as the program has matured over six breeding cycles. Average predicted gains from selection accumulated over five cycles were 143, 181 and 60% respectively, for seed yield per head, percent naked seed and mass per seed. We did not detect negative correlations that would indicate simultaneously achieving increased grain yield and sustained perenniality would be particularly difficult. Heritability estimates based on genetic markers were the same or higher than those calculated from a pedigree, indicating that markers have potential to expedite breeding efforts.