Transitions towards higher levels of sustainability have been subject of many investigations, both theoretically and empirically. While the focus has been on the scale of national innovation systems and technology systems, the quality of space (place) with regard to regions and cities has received scarce attention or no attention at all, thereby overlooking spatial specificities that may enhance or block pathways towards transition. This paper deals with sustainability innovators among young high-tech companies, as spin-offs from universities. They mainly deal with sustainable energy, sustainable transport, and healthcare. It explores whether the character of the city of location and of networks of these companies make a difference in growth and potential contribution to transitions. The paper starts with a conceptual reflection on what the role of cities as seedbeds including nodes of networks may be according to various spatial-theoretical perspectives. The paper proceeds with an exploratory analysis of growth among innovators (spin-offs) in two different cities in Europe, in a core metropolitan area and a rather peripheral region, and with an analysis of the network types and city characteristics involved. We use a sample of 60 companies in a comparative analysis and regression modeling in the first part and retrospective descriptive analysis of five case studies in the second part of the paper. It appears that companies dealing with sustainability innovations grow quicker and benefit stronger from diversity in networks in a metropolitan city compared to a peripherally located city. At the same time there is a trend of adaptation of location, like building a multi-site company and connecting with partners locally and globally. Aside from spatial influences there is the role of the national innovation system, particularly public policy in favor of particular sustainability inventions and enhancing niche development. If favorable national policies are abandoned, university spin-offs as vulnerable companies, tend to broaden their focus and diversify in products and markets in order to survive, thereby reducing the chance of contributing to pathways to sustainability. The paper concludes with implications and research needs.