Mutualistic plant–microbial functioning relies on co-adapted symbiotic partners as well as conducive environmental conditions. Choosing particular plant genotypes for domestication and subsequent cultivar selection can narrow the gene pools of crop plants to a degree that they are no longer able to benefit from microbial mutualists. Elevated mineral nutrient levels in cultivated soils also reduce the dependence of crops on nutritional support by mutualists such as mycorrhizal fungi and rhizobia. Thus, current ways of crop production are predestined to compromise the propagation and function of microbial symbionts, limiting their long-term benefits for plant yield stability. The influence of mutualists on non-native plant establishment and spread, i.e. biological invasions, provides an unexplored analogue to contemporary crop production that accounts for mutualistic services from symbionts like rhizobia and mycorrhizae. The historical exposure of organisms to biotic interactions over evolutionary timescales, or so-called eco-evolutionary experience (EEE), has been used to explain the success of such invasions. In this paper, we stress that consideration of the EEE concept can shed light on how to overcome the loss of microbial mutualist functions following crop domestication and breeding. We propose specific experimental approaches to utilize the wild ancestors of crops to determine whether crop domestication compromised the benefits derived from root microbial symbioses or not. This can predict the potential for success of mutualistic symbiosis manipulation in modern crops and the maintenance of effective microbial mutualisms over the long term.