Associative theories of creativity argue that creative cognition involves the abilities to generate remote associations and make useful connections between unrelated concepts in one’s semantic memory. Yet, whether and how real-life creative behavior relies on semantic memory structure and its neural substrates remains unclear. We acquired multi-echo functional magnetic resonance imaging data while participants underwent a semantic relatedness judgment task. These ratings were used to estimate their individual semantic memory networks, whose properties significantly predicted their real-life creativity. Using a connectome predictive modeling approach, we identified patterns of task-based functional connectivity that predicted creativity-related semantic memory network properties. Furthermore, these properties mediated the relationship between functional connectivity and real-life creativity. These results provide new insights into how brain connectivity patterns support real-life creative behavior via the structure of semantic memory. We also show how computational network science can be used to couple behavioral, cognitive, and neural levels of analysis.