Data about points of interest (POI) have been widely used in studying urban land use types and for sensing human behavior. However, it is difficult to quantify the correct mix or the spatial relations among different POI types indicative of specific urban functions. In this research, we develop a statistical framework to help discover semantically meaningful topics and functional regions based on the co‐occurrence patterns of POI types. The framework applies the latent Dirichlet allocation (LDA) topic modeling technique and incorporates user check‐in activities on location‐based social networks. Using a large corpus of about 100,000 Foursquare venues and user check‐in behavior in the 10 most populated urban areas of the US, we demonstrate the effectiveness of our proposed methodology by identifying distinctive types of latent topics and, further, by extracting urban functional regions using K‐means clustering and Delaunay triangulation spatial constraints clustering. We show that a region can support multiple functions but with different probabilities, while the same type of functional region can span multiple geographically non‐adjacent locations. Since each region can be modeled as a vector consisting of multinomial topic distributions, similar regions with regard to their thematic topic signatures can be identified. Compared with remote sensing images which mainly uncover the physical landscape of urban environments, our popularity‐based POI topic modeling approach can be seen as a complementary social sensing view on urban space based on human activities.