The London plane (Platanus × acerifolia (Aiton) Willd.) street tree is a symbolic tree species in Nanjing City, which is known as the “city card”. However, accidents such as street trees falling over cars, affecting traffic, and hurting people have seriously affected the daily lives of citizens. Thus, it is of vital significance to accurately assess the potential for tree failure in London plane street trees in Nanjing City. This study comprehensively considers the growth condition of London plane street trees and their impact on traffic, establishes a scientific street tree failure assessment scheme that contains eight characteristics, creates a tree failure assessment database by thoroughly collecting data on trees, and develops a tree failure assessment model based on factor analysis and k-means clustering. The assessment results show that street trees that pose a high or medium potential for failure are present in proportions of 4.47% and 34.85%, respectively, and are mostly found in Gulou District, Xuanwu District, and Qinhuai District. The average tree failure score of London plane street trees on Changjiang Road in Xuanwu District is the highest, while the road with the lowest tree failure score is Mufu East Road in Gulou District. The results will provide a scientific basis for the maintenance of London plane street trees in Nanjing City and have reference significance for other street tree failure assessment studies.