Countries around the world are devising and implementing bioeconomy strategies to initiate transformation towards sustainable futures. Modern concepts of bioeconomy extend beyond bio-based energy provision and include: (1) the substitution of fossil resource-based inputs to various productive sectors, such as the chemical industry and the construction sector, (2) more efficient, including new and cascading uses of biomass, and (3) a low bulk, but high-value biologisation of processes in agro-food, pharmaceutical, and recycling industries. Outcomes of past attempts at engineering transformation, however, proved to be context-dependent and contingent on appropriate governance measures. In this paper we theoretically motivate and apply a system-level theory of change framework that identifies central mechanisms and four distinct pathways, through which bio-based transformation can generate positive or negative outcomes in multiple domains of the Sustainable Development Goals. Based on emblematic examples from three bio-based sectors, we apply the framework illustrating how case-specific mixes of transformation pathways emerge and translate into outcomes. We find that the observed mixes of transformation pathways evoke distinct mechanisms that link bioeconomic change to sustainability gains and losses. Based on this insight we derive four key lessons that can help to inform the design of strategies to enable and regulate sustainable bioeconomies.