With the increasing shift from STEM to STEAM education, arts-based approaches to science teaching and learning are considered promising for aligning school science curricula with the development of twenty-first century skills, including creativity. Yet the impact of STEAM practices on student creativity and specifically on how the latter is associated with science learning outcomes have thus far received scarce empirical support. This paper contributes to this line of research by reporting on a two-wave quantitative study that examines the effect of a long-term STEAM intervention on two cognitive processes associated with creativity (act, flow) and their interrelationships with intrinsic and extrinsic components of science motivation. Using pre- and post-survey data from 175 high-school students in Italy, results show an overall positive effect of the intervention both on the act subscale of creativity and science career motivation, whereas a negative effect is found on self-efficacy. Gender differences in the above effects are also observed. Further, results provide support for the mediating role of self-efficacy in the relationship between creativity and science career motivation. Implications for the design of STEAM learning environments are discussed.