Novelty is an essential feature of creative ideas, yet the building blocks of new ideas are often embodied in existing knowledge. From this perspective, balancing atypical knowledge with conventional knowledge may be critical to the link between innovativeness and impact. The authors’ analysis of 17.9 million papers spanning all scientific fields suggests that science follows a nearly universal pattern: The highest-impact science is primarily grounded in exceptionally conventional combinations of prior work, yet simultaneously features an intrusion of unusual combinations. Papers of this type were twice as likely to be highly cited works. Novel combinations of prior work are rare, yet teams are 37.7 % more likely than solo authors to insert novel combinations into familiar knowledge domains.