The search for approaches to a holistic sustainable agriculture requires the development of new cropping systems that provide additional ecosystem services beyond biomass supply for food, feed, material, and energy use. The reduction of chemical synthetic plant protection products is a key instrument to protect vulnerable natural resources such as groundwater and biodiversity. Together with an optimal use of mineral fertilizer, agroecological practices, and precision agriculture technologies, a complete elimination of chemical synthetic plant protection in mineral-ecological cropping systems (MECSs) may not only improve the environmental performance of agroecosystems, but also ensure their yield performance. Therefore, the development of MECSs aims to improve the overall ecosystem services of agricultural landscapes by (i) improving the provision of regulating ecosystem services compared to conventional cropping systems and (ii) improving the supply of provisioning ecosystem services compared to organic cropping systems. In the present review, all relevant research levels and aspects of this new farming concept are outlined and discussed based on a comprehensive literature review and the ongoing research project “Agriculture 4.0 without Chemical-Synthetic Plant Protection”.