Shifting the life cycle of grain crops from annual to perennial would usher in a new era of agriculture that is more environmentally friendly, resilient to climate change, and capable of soil carbon sequestration. Despite decades of work, transforming the annual grain crop wheat (Triticum aestivum) into a perennial has yet to be realized. Direct domestication of wild perennial grass relatives of wheat, such as Thinopyrum intermedium, is an alternative approach. Here we highlight protein coding sequences in the recently released T. intermedium genome sequence that may be orthologous to domestication genes identified in annual grain crops. Their presence suggests a roadmap for the accelerated domestication of this plant using new breeding technologies.