Our research aims to establish an evaluation framework and evaluate the sustainability of scientific research in universities. Based on the concept of Education for Sustainable Development and the function of scientific research activities, an evaluation framework was constructed including three dimensions: the sustainable trend of scientific research activity, research performance related to the topic of sustainable development, and sustainability of scientific research contributions. Descriptive analysis, Data Envelopment Analysis, and a Statistical Index Method were used to calculate the sustainability of scientific research of world-class universities in China. Results show that China’s world-class universities published more articles related to sustainable development than the best-performing universities in the UK and USA. They make sustainable contributions to society through cultivating Ph.D. graduates, publishing research papers, and transforming science and technology. However, the sustainable trend of the scientific research of universities is still to be improved. The result of resource efficiency is relatively low, and attention should be paid to the waste of human and financial resources. In addition, universities should improve their ability to withstand external risks to minimize the influence of external public emergencies such as COVID-19.