Knowledge networks are now recognised as a crucial element underlying the economic success and competitiveness of geographic locations, in particular regions. The aim of this paper is to assess the types of knowledge networks utilised and formed by knowledge-based small- and medium-sized enterprises (SMEs) in the relatively uncompetitive regional setting of Yorkshire and Humberside in the UK. It explores the relationship between knowledge networking activity and the levels of innovation and growth achieved by these SMEs. It is found that SMEs tend to utilise and value more knowledge networks with actors outside the region. However, more innovative SMEs possess a balance of inside and outside the region knowledge networks. Knowledge networking activity is sometimes negatively associated with growth, suggesting that networks with certain actors, such as public sector support agencies, may be formed by SMEs when they are facing competitive pressures. In terms of policy implications, the paper recommends a shift from the cluster policies implemented by many regional authorities to a regional innovation systems approach, focusing equally on the regional and more global dimensions of knowledge networks. It is concluded that regional public policy makers need to renew their efforts to support SMEs in creating and sustaining their knowledge networks.