Abstract: Against the backdrop of innovative development strategy and knowledge economy, intercity knowledge flows have become an important perspective to explore intercity relationship and spatial reconstruction. Therefore, knowledge collaboration network based on scientific co-publications has attracted much attention. Based on scientific publication data during 2015-2019 derived from Web of Science, the intercity knowledge collaboration network of the Yangtze River Delta (YRD) was constructed by employing crawler technology, in which nodes represented cities at the prefecture level and above. After that, spatial patterns and influencing factors were analyzed through the lens of dyadic strength, node centrality, and QAP regression. The results have shown that: (1) Knowledge flows in YRD is concentrated in the Z-shape development corridor of Shanghai-Nanjing-Hefei-Hangzhou-Ningbo, presenting obvious “rich-club” phenomenon. Nanjing has the strongest knowledge productivity and control power in YRD. The intercity collaboration between Jiangsu and other cities is relatively high and balanced, showing a multi-polar development. The intercity collaboration in Anhui is sparse, which mainly depends on the development of Hefei’s external collaboration. Zhejiang’s situation lies in between and the intercity collaboration is organized by Hangzhou and Ningbo. (2) Population, R&D, universities have a positive effect on intercity knowledge collaboration, among which universities have the strongest and most significant impact. The distance decay still exists, and administrative boundary could hinder intercity collaboration to some extent, but it’s effect is much smaller than the distance damping. Cultural proximity has no significant impact on knowledge collaboration, whereas administrative hierarchy matters.