Abstract The concept of a location's irreplaceability pertains to its unique characteristics that make it challenging for other locations to replace in terms of providing services and meeting needs. While scholars have shown great enthusiasm for studying location irreplaceability, accurately measuring it and understanding the effects of urban form have not been thoroughly explored through empirical research. This study selects Shenzhen, China, as the study area. First, the I ‐index, which focuses on geographic flow, is utilized to measure the location's irreplaceability using mobile phone data. Subsequently, the factors related to urban form are analyzed from the perspectives of demography, building capacity, public services, and the location's conditions. Finally, a geographically and temporally weighted regression model (GTWR) is constructed to explore the spatiotemporal relationships between irreplaceability and urban form. The study demonstrates that the I ‐index, considering flow volume and distance, can effectively measure the location's irreplaceability. The results of GTWR indicate that the location's irreplaceability and its influencing factors exhibit spatiotemporal heterogeneity. This study advances our understanding of the relationships between location irreplaceability and urban form both conceptually and methodologically. The findings have practical implications for urban design and planning, including urban space optimization, facility equity, and the alleviation of traffic congestion.