The micro-level urban morphology of large cities in the Middle East and North Africa and southeastern Europe has not been thoroughly investigated, and its transformation during the past decades has remained less-studied. Hence, this study is meant to partially explain urban morphology of Istanbul, Cairo, and Tehran, three megacities of the region by focusing on the historical neighborhood typologies of the past century. The overall aim of this study is to address the feedbacks of historical urban transformations during the past 100 or 150 years to some important aspects of livability like mobility and social interactions. The objectives are to define the typologies of neighborhoods in the three cities and how they have changed over time, to clarify if the neighborhood-level urban form of the three cities have transformed in a similar fashion, and to address the differences between the cities. The variables of this study were population density, centrality, formation and location of facilities, and configuration of street networks, which were tested by T and Chi-square methods in a representative sample of 259 neighborhoods randomly selected from the case-study cities. The results of statistical hypothesis testing reveal a similarity of neighborhood transformations in the cities in terms of population density. Considerable similarities were found in case of historical changes in centrality (the centeredness of neighborhood amenities), location of neighborhood facilities, and street networks; however, the three cities have general similarities in trends, with potentially similar results for urban mobility. The most important identified planning, political, and societal trends that transformed the neighborhood morphologies were top-down interventions in the 1930s and 1940s, socioeconomic and lifestyle changes in the 1970s because of a jump in oil prices, Iran's 1979 revolution, the Iran-Iraq War for Tehran, internal migration triggered by industrialization, mass and formal housing production for Istanbul, and European inspiration in urban planning in the late 19th century, adoption of socialist ideologies in the 1960s, and the capitalist approach to urban planning in recent years for Cairo.