Buildings in high-income, industrialized cities are responsible for more than 50% of global energy consumption; consequently, many developed cities have legislated energy benchmarking and disclosure policies to understand their buildings’ energy-use dynamics better. By utilizing these benchmarking data and additional information taken from 3D models, this paper presents a comprehensive analysis of large-scale office buildings located in New York and Chicago, with respect to their energy use intensity (EUI). To identify the primary factors affecting the EUI, Spearman’s correlation analysis and multiple variate regression tests were performed on office buildings over 500,000 ft2 (46,452 m2) gross floor area. The results showed the number of floors, construction year, window-to-wall ratio (WWR), and source-to-site ratio statistically significant, while morphological factors such as the relative compactness and surface-to-volume ratio showed limited relation to EUI. In New York City, the smallest EUI median was found in the buildings with 20 to 30 floors, and in Chicago, the buildings with 60 floors or more. A higher source-to-site ratio generally had lower overall EUI in both cities. Despite the high correlation, different kinds of dependency were found for window-to-wall ratio (WWR) and construction year between NYC and Chicago. These findings highlight the relative role that each building’s characteristics play concerning the EUI, depending on the particular building’s typology, scale, and the urban context.