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The national project «Small and medium-sized entrepreneurship and support for individual entrepreneurial initiative» has identified very ambitious targets for achieving by 2024, including: the number of people employed in the field of small and medium-sized businesses — 25 million people. It is impossible to solve the tasks set, taking into account the demographic problems of Russia, as well as to ensure the implementation of the priorities of scientific and technical development of the country, without the active involvement of young people in business activities. The formation of an appropriate environment in universities is one of the mechanisms for the development of young people entrepreneurial activity. The purpose of the research is to substantiate the activation directions of mechanisms for the development of youth entrepreneurship in Russian universities. The ecosystem approach was the theoretical basis. The methodological basis was general scientific methods: comparative analysis, content analysis, grouping method. An analysis of the supporting and developing entrepreneurial initiatives experience of in the foreign educational institutions — Stanford University, Catholic University of Leuven and Pohang University of science and technology — showed that success is largely determined by the presence of an effective partnerships system, primarily with business representatives. In this regard, 10 Russian universities that occupy leading positions in the QS 2019 international ranking were analyzed using the author’s previously developed methodology for evaluating the effectiveness of a comprehensive mechanism for developing youth entrepreneurship based on interaction with partners. The scientific novelty of the presented research results consists in the selection based on the results of the assessment of four universities groups: 1) with a relatively uniform development of various areas (education, infrastructure, popularization), 2) with a priority on the practical component, 3) with an emphasis on educational content and popularization, 4) with the implementation of individual entrepreneurial initiatives of young people. The directions of mechanisms activation of the youth entrepreneurship development are formed taking into account the selected universities groups. At the same time, for each of them, the emphasis is on the need to attract more partners for the development of youth entrepreneurial initiatives, especially given the limited University resources.