Australia has a diverse and unique native flora with thousands of edible plant taxa, many of which are wild relatives of important food crops. These have the potential to diversify and improve the sustainability of Australian farming systems. However, the current level of domestication and cultivation of Australian plants as food crops is extremely limited by global standards. This review examines the current status and potential for future de novo domestication and large-scale cultivation of Australian plants as food crops. This is done in the context of international new crop development and factors that impact the success or failure of such efforts. Our review finds considerable potential for native Australian plants to be developed as food crops, but the industry faces several significant challenges. The current industry focuses on niche food markets that are susceptible to oversupply. It also suffers from inconsistent quantity and quality of product, which is attributed to a reliance on wild harvesting and the cultivation of unimproved germplasm. More active cultivation is necessary for industry growth, but attempts have historically failed due to poorly adapted germplasm and a lack of agronomic information. The de novo domestication and large-scale cultivation of Australian plants as food crops will require an investment in publicly supported multidisciplinary research and development programmes. Research programmes must prioritize the exploration of plants throughout Australia and the collection and evaluation of germplasm. Programmes must also seek to engage relevant stakeholders, pursue participatory research models and provide appropriate engagement and benefit-sharing opportunities with Indigenous Australian communities.