Subject. In recent years, in the strategic documents of the state, emphasis has been placed on the spatial development of Russian regions. The conditions of global economic challenges and restrictive sanctions increase the importance of innovation in the spatial development of regions. The goal is to substantiate the dominant nature of innovation activity in ensuring the spatial development of the region. Methodology. In the process of research, theoretical methods of scientific knowledge, methods of analysis and synthesis were used. The methodological basis of the study is the works of domestic and foreign authors devoted to innovation and spatial development of the region. Results. The paper substantiates the relationship between the concepts of innovation, the innovation process and innovation activity, which served as the basis for the author's formulation of the concept of innovation activity in the region (a set of activities aimed at organizing and implementing innovation processes, as well as providing conditions for their effective implementation through the creation and development innovation infrastructure). The concept of innovation infrastructure as a set of organizations created within the framework of organizational measures of state support, whose activities are aimed at ensuring innovation processes, has been clarified. From the position of the innovative aspect, the concept of spatial development of the region is defined as a process of achieving the economic and social attractiveness of the region through territorial innovative transformations, the result of which is a new qualitative level of socio-economic processes, interconnected and organized through management processes carried out within the boundaries of the territory and taking into account nationwide priorities. The dominant influence of innovation activity on the spatial development of the region is due to the resulting effects: increasing the level of manufacturability of economic entities; raising the level of development of productive forces; capitalization of labor resources; creation of new competitive sectors of the regional economy and others. The principles of innovative activity in the direction of the spatial development of the region (the principle of taking into account national priorities; the principle of cooperation; the principle of scientific character; the principle of market expediency and others) are proposed.