Creative thinking is important for success in the fields of science, technology, engineering, and mathematics (STEM). Yet creativity in STEM is perhaps the most under-researched question in the creativity literature, with little known about the neurocognitive mechanisms supporting scientific creative thinking abilities, such as hypothesis generation. In the present functional magnetic resonance imaging study, undergraduate STEM majors (n = 47) completed a scientific hypothesis generation task (thinking of novel/plausible explanations for hypothetical scenarios) and a control task (thinking of synonyms to replace a word in a hypothetical scenario). Multivariate pattern analysis identified a whole-brain network supporting hypothesis generation, including hubs of the default (posterior cingulate cortex [PCC]), salience (right anterior insula [AI]), and semantic control (left inferior frontal gyrus [IFG]) networks. Using these network hubs as seed regions, we found increased between-network functional connectivity during hypothesis generation, including stronger coupling between semantic control (IFG) and posterior default regions (PCC and bilateral angular gyrus) and stronger coupling between salience (AI) and default regions, alongside weaker within-network functional connectivity. Our results indicate that scientific creative thinking involves increased cooperation among the default, salience, and control networks—similar to creative thinking in other domains—potentially reflecting a coordination of spontaneous/generative and controlled/evaluative processes to construct original explanations for scientific phenomena.