Sustainable development and the definition of indicators to assess progress towards sustainability have become a high priority in scientific research and on policy agendas. In this paper, we propose a consistent and comprehensive framework of principles, criteria and indicators (PC&I) for sustainability assessment of agricultural systems, referred to as the Sustainability Assessment of Farming and the Environment (SAFE) framework. In addition we formulate consistent and objective approaches for indicator identification and selection. The framework is designed for three spatial levels: the parcel level, the farm level and a higher spatial level that can be the landscape, the region or the state. The SAFE framework is hierarchical as it is composed of principles, criteria, indicators and reference values in a structured way. Principles are related to the multiple functions of the agro-ecosystem, which go clearly beyond the production function alone. The multifunctional character of the agro-ecosystem encompasses the three pillars of sustainability: the environmental, economic and social pillars. Indicators and reference values are the end-products of the framework. They are the operational tools that are used for evaluating the sustainability of the agro-ecosystems. The proposed analytical framework is not intended to find a common solution for sustainability in agriculture as a whole, but to serve as an assessment tool for the identification, the development and the evaluation of agricultural production systems, techniques and policies.