Improvements in nitrogen use efficiency in crop production are critical for addressing the triple challenges of food security, environmental degradation and climate change. Such improvements are conditional not only on technological innovation, but also on socio-economic factors that are at present poorly understood. Here we examine historical patterns of agricultural nitrogen-use efficiency and find a broad range of national approaches to agricultural development and related pollution. We analyse examples of nitrogen use and propose targets, by geographic region and crop type, to meet the 2050 global food demand projected by the Food and Agriculture Organization while also meeting the Sustainable Development Goals pertaining to agriculture recently adopted by the United Nations General Assembly. Furthermore, we discuss socio-economic policies and technological innovations that may help achieve them.