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Novelty, disruption and impact are essential concepts for understanding the originality and importance of scientific discoveries. By drawing on a large-scale corpus consisting of nearly 0.9 million PubMed papers published between 1970 and 2009 and their citations before 2018 in the Web of Science, we found that the topic-combination novelty has different effects on the impact and disruption of scientific papers, that is, an inverted U-shaped effect on the impact and a positive effect on disruption. One of our contributions is that we have significantly improved the reliability of topic-combination novelty by applying MeSH terms of PubMed to the measurement of novelty. Another contribution is that we have explained how a novel combination of MeSH terms of an article contributes to citations and citation networks, that is, the middle-level novelty is more likely to achieve large citation counts. In contrast, high topic-combination novelty relates to the discontinuity in the focal paper’s citation network.