The locations of Fortune 500 corporate headquarters in U.S. cities spectacularly changed between 1970 and 2020. Previous researchers pointed on the diversity of business and financial services, agglomeration effects of the headquarters themselves and the role of airports as the leading factors in the localization of headquarters in the largest cities. However, factors that allow smaller agglomerations to also localize headquarters were also emphasized: proximity to the companies’ production facilities, the growth of passenger air connectivity, the opportunity to obtain more favorable local tax and regulatory conditions, more flexible cost of living for employees. Based on the Fortune 500 rating data, we analyzed the changing detailed geography of the headquarters locations of the largest American companies by MSAs by calculating the dynamics of the Shannon diversity index by economic sectors over the past 40 years. The share of headquarters of the largest corporations located in the top 50 MSAs has remained almost unchanged, but since 2000 the top 5 MSAs have been declining, while the share of MSAs in the second population quartile has increased. This trend towards deconcentration and the rise of second-order agglomerations contradicts S. Sassen’s hypothesis on the concentration of headquarters in several largest cities. The reasons for the deconcentration seem to be associated with the rise of new economic centers in the cities of the US South and West and the relocation of the headquarters of existing F?500 companies to this new centers, as well as the concentration of new industries in new places, not in the key centers of old industries. The economic diversity of headquarters has also undergone significant changes. If in 1980 the MSA New York was significantly ahead of all the others in terms of the number of headquarters and their diversity index, then by 2019 MSA Chicago was significantly closer to it in terms diversity index. At the same time, other agglomerations of Megalopolis (MSAs of Bridgeport, Richmond, Washington, etc.) of the Northeast of the United States, since 2000, have increased the diversity of headquarters, demonstrating independent growth dynamics despite the location in close proximity to the dominant MSA New York. They, as well as the fast-growing MSAs of Miami, Phoenix, San Jose, Denver, Raleigh and Winston-Salem, by 2019 showed the greatest industry diversification. Mono-specialization is not generally typical of large concentrations of headquarters, exceptions are the center of oil production, oil refining and chemical industry Houston, car manufacturing capital of Detroit and the center of Silicon Valley San Jose, the rapid growth of industrial diversity of which, however, did not allow reaching average diversity indicators.