As the world population and food production demands rise, keeping agricultural soils and landscapes healthy and productive are of paramount importance to sustaining local and global food security and the flow of ecosystem services to society. The global population, expected to reach 9.7 billion people by 2050, will put additional pressure on the available land area and resources for agricultural production. Sustainable production intensification for food security is a major challenge to both industrialized and developing countries. The paper focuses on the results from long-term multi-factorial experiments involving tillage practices, crop rotations and fertilization to study the interactions amongst the treatments in the context of sustainable production intensification. The paper discusses the results in relation to reported performance of crops and soil quality in Conservation Agriculture systems that are based on no or minimum soil disturbance (no-till seeding and weeding), maintenance of soil mulch cover with crop biomass and cover crops, and diversified cropping s involving annuals and perennials. Conservation Agriculture also emphasizes the necessity of an agro-ecosystems approach to the management of agricultural land for sustainable production intensification, as well as to the site-specificity of agricultural production. Arguments in favor of avoiding the use of soil tillage are discussed together with agro-ecological principles for sustainable intensification of agriculture. More interdisciplinary systems research is required to support the transformation of agriculture from the conventional tillage agriculture to a more sustainable agriculture based on the principles and practices of Conservation Agriculture, along with other complementary practices of integrated crop, nutrient, water, pest, energy and farm power management.