Sustainability is a topic that is at the center of current discussions in the political, economic, social, and environmental fields. For its analysis, an integral and multidisciplinary vision is needed. This work aims to assess the sustainability of agricultural systems in Paraguay through a comparison applying SAFA (Sustainability Assessment of Food and Agriculture Systems) indicators. The research focuses on 15 case studies on the territory of the Eastern Region of Paraguay divided into five classes of agricultural systems: agribusiness, conventional peasant family farming, agroecological peasant family farming, neo-rural farming, and indigenous agriculture. Data were collected through interviews with producers and key informants, direct observation, and scientific literature research in order to assess, through the SAFA Tool Software, the level of sustainability of each agricultural system as a whole and for each sustainability dimension (political, environmental, economic, and social dimension) in a comparative way. It has emerged that producers belonging to conventional peasant family farming, agroecological peasant family farming, neo-rural farming, and indigenous agriculture have achieved levels of sustainability that are similar to each other and very good in all four dimensions of sustainability. Meanwhile, agribusiness achieved moderate scores in the dimensions of governance and environmental integrity, and was good in the economic and social dimension.