Exploring the relationship between urban spatial growth and population density change is the basis of urban sustainable development research, which is of great significance for formulating effective land policies to promote urban compact development. The research selected 23 cities with a population of more than 1 million in China and Europe as the study areas. Based on the land use and population data in the study areas in 1990, 2000, and 2014, the research calculated the growth rate of sample urban space during each period, and the urban compactness index was then established to divide the urban spatial growth mode into compact type, maintenance type and spread type. The characteristics of spatial growth, population density change, and their relationship were further discussed. The results are as follows: (1) Population density decline is widespread in cities of China and Europe. Population density in cities of China is relatively high, and the rate of decline is fast, whereas population density in cities of Europe is relatively low and the rate of decline is slow. From 1990 to 2014, the growth rate of urban spatial radius in China was significantly higher than that in Europe. There is a strong negative correlation between the growth rate of urban space and the change rate of population density (with a Pearson's r of -0.693). (2) From 1990 to 2000, most of the sample cities' spatial growth mode were compact. From 2000 to 2014, most Chinese cities' spatial growth mode transformed into spread type and rate of population density decline increased. By contrast, European cities' spatial growth mode maintained to be compact or transformed into maintenance, and the rate of population density decline decreased. (3) Compact spatial growth does not necessarily lead to an increase in population density, but it tends to lower the rate of population density decline, relative to spread spatial growth. The comparative analysis of Chinese and European cities shows that if cities maintain a compact spatial growth mode, the rate of population density will be lowered. If cities' spatial growth mode transforms from compact to spread, it will intensify the decline of urban population density over time.