Amid growing inter-state competition, national innovation policies are increasingly seeking to promote the development of regional innovation systems to intensify innovative processes and to enhance the economic competitiveness of territories. An efficient regional innovation policy requires a territorial adaptive approach to the development of mechanisms for innovating socio-spatial systems. These mechanisms should take into account the specific features and inalienable resources of territories. Whereas regional innovation systems are becoming increasingly acknowledged in public administration as versatile, the stage of a system life cycle, which is an equally important factor, often escapes managerial attention. In this article, I analyse the innovation system of the Kaliningrad region at its inception. The Kaliningrad case is of considerable interest for a study into the patterns and characteristics of the governance of innovation systems — a management paradigm aimed to promote regional development during a change in their functioning mode. In this work, I analyse the current structure of the Kaliningrad regional innovation system, of which some elements date back to the Soviet period, paying particular attention to the subsequent change in the framework conditions. I show that a new innovation trajectory requires taking into account the economic and geographical position of the region, its level of socio-economic development and economic specialization. My findings could contribute to both improving the national policy on managing innovation processes in Russian regions and developing the concept of regional innovation systems as regards research into their life cycle stages.