Current food systems are challenged by relying on a few input-intensive, staple crops. The prioritization of yield and the loss of diversity during the recent history of domestication has created contemporary crops and cropping systems that are ecologically unsustainable, vulnerable to climate change, nutrient poor, and socially inequitable. For decades, scientists have proposed diversity as a solution to address these challenges to global food security. Here, we outline the possibilities for a new era of crop domestication, focused on broadening the palette of crop diversity, that engages and benefits the three elements of domestication: crops, ecosystems, and humans. We explore how the suite of tools and technologies at hand can be applied to renew diversity in existing crops, improve underutilized crops, and domesticate new crops to bolster genetic, agroecosystem, and food system diversity. Implementing the new era of domestication requires that researchers, funders, and policy makers boldly invest in basic and translational research. Humans need more diverse food systems in the Anthropocene–the process of domestication can help build them.