Based on the data of China’s top 100 packaging and printing enterprises, the spatial and temporal evolution characteristics and influencing factors of China’s top 100 packaging and printing enterprises are systematically analyzed using standard deviation ellipsoids, kernel density estimation, hot spot analysis and GeoDetector. The results show that: 1) From 2012 to 2022, China’s top 100 packaging and printing enterprises show a trend of spreading from the coast to the inland. 2) Top 100 packaging and printing enterprises have obvious spatial clustering characteristics east of the Hu Line, with the Yangtze River Delta and the Pearl River Delta being the main distribution sites. 3) The distribution of cold and hot spots is relatively stable in the last decade, with hot spots and sub-hot spots mainly located in Henan, Anhui, Hubei, Zhejiang, Guangdong and Shandong, and cold spots in the northwestern and northeastern. 4) The spatial distribution of top 100 packaging and printing enterprises is mainly affected by factors such as international trade level, labor force, regional economic strength and regional policies, and the influence of market scale on the spatial distribution of top 100 enterprises in the packaging and printing sector has gradually increased. Compared with the independent effect of a single factor, the influence of two influencing factors is stronger when they interact.