The ability to identify and foster innovative solutions to complex challenges is critically important in regional Australia, and particularly so in ‘resource regions’. This paper explores the role for innovation in delivering regional outcomes across the social, economic and environmental domains. It describes the value of regional innovation strategies in assessing regional assets, challenges and emerging opportunities, through a case study focus on Central Queensland. This region is one of Australia’s key resource hubs, which benefits from the economic activity linked with extractive, transport and processing industries, but also experiences a range of adverse social and environmental effects. Awareness of innovation systems and innovative practices allows regional development practitioners, as well as the mining industry itself, to re-frame issues and opportunities beyond current drivers, development paradigms and planning horizons. The paper presents a set of innovation-based principles to consider when developing strategic responses to these challenges and opportunities. It also introduces the concept of ‘innovation wedges’ to strengthen regional capacity to adjust and adapt to the rapid and cumulative impacts of resource development activity.